Korean, Edit

Chapter 5. Cell division and Cancer

Higher category : 【Biology】 Biology Index 

1. DNA and Chromosomes

2. Vertical transfer of genes

3. Cell cycle regulation

4. Cancer

5. The occurrence of cancer

6. Cancer discovery and treatment

a. Horizontal Transfer of Genes

1. DNA and Chromosomes

⑴ DNA binds to proteins to form a dye (= chromatin) and contains many genes

① Cationic amino acids, such as histidine, condense negatively charged DNA

② Heterochromatin : Condensation of chromatin

③ Soothing dye : Chromatin loose

⑵ Chromosome : Condensation of chromatin and observable with optical microscope

① Number of chromosomes = Number of chunks acting as one = Number of chunks that are dyed together

② The number of chromosomes is equal to the number of allotopics except tetravalent chromosomes ⑶ Karyotype : Refers to the shape, size and number of chromosomes, species specific

① Use chemicals to stop during cell division for observation

⑷ Sister chromatids : Chromosomes bound to each other at the centromere after the non-replicated chromosome is replicated

① The number of sister chromosomes is the number of DNA

② Mobilization : Possibility of dynein motor protein binding site and mobilization

③ Divalent Chromosome (chromosome tetrad) : If there are four sister chromosomes on one chromosome, four sister chromosomes bound to the centromere

○ Homologous chromosomes do not share isotopes : The number of chromosomes = why the number of chromosomes

○ 1 divalent chromosome = 1 chromosome tetrad = 2 chromosomes = 4 sister chromosomes

④ Monovalent chromosome (chromosome dyad) : If there are two sister chromosomes on a chromosome, two sister chromosomes bound to the centromere  

○ Respectively called P arm and Q arm

○ 1 monovalent chromosome = 1 chromosome dyad = 1 chromosome = 2 sister chromosomes

⑤ Zero-valent chromosome : If one chromosome has one sister chromosome, one strand of DNA double helix

○ Chromosome Forms of Germ Cells

○ 1 zero chromosome = 0 chromosomes = 1 sister chromosome

⑸ Homologous and sex chromosomes

① Homologous chromosome (autosome) : Same size, shape, centroid position, relative locus (locus, locus)

② Sex chromosome : Different positions, genetic makeup, partial homology

③ Example : Humans have 22 pairs of autosomal and 1 pair of sex chromosomes

④ Example : Human germ cells have 22 autosomal and 1 sex chromosomes

⑹ Cell division involved protein

① condensin (condensin) : Condensing Dyed Yarns to Chromosomes

② Cohesion : Each chromosome binds to each other, only cohesins exist near the centromere

③ Shugosin : Do not decompose homologous chromosomes in 1meiosis

④ Securin : Inhibition of seperase, prevention of separation of sister chromosome until late cell division

○ It acts on mitosis, meiosis and meiosis

○ APC Inhibits Securin

⑤ seperase (seperase) : Decomposition of cohesins of isotope subgroups, and separation of sister chromosome in late cell division

○ It acts on mitosis, meiosis and meiosis

⑺ Mitotic spindle

① Spinal cord is composed of microtubules

② Spinal cord attachment point (kinetochore) : Structure that protein binds to isotope

③ Kinetochore microtubule : Dynein, spindle splice bound to chromosomes, involved in late chromosomal migration

④ Nonkinetochore microtubule : Pair of kinesins, spindles with opposite spindles, involved in terminal cell extension

○ One kinesin of each polar spine sticks together and pushes each other

⑤ Astral Skewers : Later transfer of centroids to the anode

⑥ Chromosomal Arm Skewers : Spinal cord attached to the arm of chromosome, rotating the chromosome later in order to orient it properly

⑻ Reagent

① Gimsa : Better staining on A-T rich sites with fewer bindings on chromosomes

② Acetic acid alcohol : Fixed to prevent cell division

③ Hydroxy Urea : Unite all cells into G1

④ Acridine orange : DNA double helix broken

⑤ Phytohemagglutinin (PHA) : Convert neutrophils into neutrophils blasts to induce division and differentiation and use for karyotyping

2. Vertical transfer of genes : Cell division

⑴ Type of cell division

① Mitosis : Somatic cell division

○ Embryogenesis, wound healing, tissue and organ production and growth in the fertilized egg

○ Daughter cells genetically identical to parental : Premise of no mutation

○ Proliferation of asexual reproduction

② Meiosis : Germ cell division

○ Cleavage for Diploid Creatures to Create Gametes for Sexual Reproduction

○ Half the number of chromosomes → daughter cells are haploids (n)

○ Methods of Proliferation of Sexual Reproduction

③ Number of chromosomes and sister chromosomes (meiosis)

⑵ Cleavage and tickling

① Interphase : Most cell cycles

○ G stands for gap or growth, S stands for synthesis

○ G1 : Cell growth and organelle proliferation

○ S group : DNA replication, centrifugal replication, histone protein synthesis. 46 chromosomes, 92 sister chromosomes / cell

○ In the case of animal cells, two centrioles form one centrosome, so the final four centroids

○ In the case of plant cells, the final two centroids

○ G2 : Proteins required for cell division (e.g., Tubulin) synthesis

② Mitotic phase

○ Nuclear fission : Chromosomes move to the anode

○ Cytoplasmic cleavage : Two cytoplasm split into two daughter cells

③ Cell fusion experiment

○ S-phase cells contain substances that promote the transfer of G1-core nuclei to S-phase.

○ S phase cells contain substances that inhibit the transfer of G2 phase nuclei to M phase.

○ In G2 cells, there is no substance that promotes the transfer of G1 nuclei to S groups.

○ Mitosis-inducing factor in M-phase cells

⑶ mitosis = nuclear fission (once) + cytoplasm

① Green fluorescent protein (GFP) : Jellyfish-derived protein widely used as a report protein that indicates the location and extent of intracellular gene expression.

② Prophase : 46 chromosomes, 92 sister chromosomes / cell

○ Phosphorus disappearance, dye dye condensation, chromosome formation

○ Kohesine binds to the sister dye powders, but the cohesins in the parts other than the isotope melt.

○ Generation of mitotic spindles from centrosomes

③ prometaphase (prometaphase) : 46 chromosomes, 92 sister chromosomes / cell

○ Nuclear film loss : prometaphase is a post-nucleus phase

○ Spinal cord microtubule reaches chromosome

○ The nuclear membrane must be lost before the spindle can reach the microtubules

○ Chromosome transfer

○ Spinach must reach microtubule to move chromosome

④ Metaphase : 46 chromosomes, 92 sister chromosomes / cell

○ The spindle is completely complete

○ All the chromosomes are arranged on the equatorial plate of cells

○ Isotopes of two sister chromosomes point to opposite poles

⑤ Anaphase : 92 chromosomes, 92 sister chromosome / cell

○ Isotopic Separation by Seperase

○ Sister chromatids move to opposite poles in a dinein on a centrifugal spindle

○ Centroid : Due to tubulin characteristics, micro-tubule decomposition occurs in the negative electrode and rapid decomposition of dynein occurs in the positive electrode.

○ As the length of the polar spindle continues to grow, the cells elongate

⑥ Telophase : 92 chromosomes, 92 sister chromosome / cell

○ Cell elongation continues

○ Nucleation is formed around the chromosome at each pole → nucleation

○ Phosphorus Remodeling, Spinal Cord Loss

○ Chromosomes are released and become dye yarns

⑦ Cytokinesis : Cellular fission occurs independently of fission

⑧ End of cell division : 46 chromosomes, 46 sister chromosome / cell

○ Cytoplasm split in half

○ Plant : Fibrous cell plate formation between two daughter cells, vesicles move along phragmoplast

○ Phragmoplast : Consists of microtubules, microfibers, and vesicles

○ Animal : Condensation of microfilament rings between the two daughter cells → cleavage furrow, outside → cytoplasm separation

⑷ meiosis = 1^st meiosis + 2^nd meiosis (mitosis of haploid)

① Prophase Ⅰ : 46 chromosomes, 92 sister chromosomes / cell

○ 1^st. Chromosomes condense and become denser, nuclear membranes disappear

○ 2^nd. Weak binding of homologous chromosomes by crossover between homologous chromosomes

○ 3^rd. Synapsis : Strong binding of chromosomes by SP (synaptonemal complex)

○ 4^th. Genetic information exchange due to crossover between homologous chromosome pairs

② Medium phase I : 46 chromosomes, 92 sister chromosomes / cell

○ Chromosome tetrad is arranged on the equator.

③ Anaphase I : 46 chromosomes, 92 sister chromosomes / cell

○ The chromosome tetrad is separated into pairs of two homologous chromosomes (chromosome dyad) and moved to opposite poles

○ chromosome tetrad : 2 chromosomes

○ chromosome dyad : 1 chromosome

④ Telophase I + cellular division : 46 chromosomes, 92 sister chromosomes / cell

○ In some organisms the nuclear membrane is reshaped, but not in humans

○ Each nucleus becomes a haploid (n)

⑤ Termination of Cell I : 23 chromosomes, 46 sister chromosome / cell

⑥ Prophase II : 23 chromosomes, 46 sister chromosome / cell

○ Second meiosis begins without an interval (chromosome replication, etc.).

○ Chromosomes condense and become dense

○ If a nuclear film is formed, it disappears again

⑦ Medium phase II : 23 chromosomes, 46 sister chromosome / cell

○ Chromosome dyad is arranged on the equator.

⑧ Anaphase II : 46 chromosomes, 46 sister chromosome / cell

○ Sister Chromosome Separated.

○ A pair of homologous chromosomes move to opposite poles.

⑨ Late phase II : 46 chromosomes, 46 sister chromosome / cell

○ After the chromosome moves to each pole, a nuclear membrane is formed around the chromosome

⑩ Termination of Cell II : 23 chromosomes, 23 sister chromosome / cell

⑪ Crossing over

○ Cross : Partial gene exchange between homologous chromosomes results in the formation of new forms of chromosomes

○ Crossing

○ Crossover rate : Classical genetics assumes that the distance between genes is proportional to the probability of their intersection..

○ About 30 crossovers occur in one meiosis.

⑫ Random sort : Alignment and isolation of each pair of homologous chromosomes during the first meiosis is independent, resulting in a variety of germ cells

⑬ Diversity of Genetic Information in Individuals (Human)

○ Chromosome Diversity of Germ Cells Resulting from First Meimeiosis : 223 + cross

○ Chromosome Diversity in Fertilized Eggs : (223 + cross) × (223 + cross)

3. Cell cycle regulation

⑴ Regulatory Proteins Control Cleavage

① Cyclin : The amount continues to change throughout the cell cycle, and at the end of each phase all associated cyclins are degraded

○ Degraded by Proteasome

② Cyclin-dependent kinase (CDK) : The amount is constant during the cell cycle, and the activity varies depending on the amount of cyclin

③ M-phase promoting factor (MPF)

○ Collectively known as CDK1 and cyclin B, are present in the cytoplasm of dividing mammalian cells

○ Role : Chromosome condensation, spindle elongation, nuclear membrane collapse

○ Spinal cord binding to isotope → APF activity → MPF inhibition

④ CDC : Substances that play an MPF role in yeast

⑤ Late phase promoter (APC, anaphase promoting complex)

○ APC (anaphase promoting complex) activity at the end of cell division → securin inhibition → seperase promotion

○ MPF Suppresses When APC Is Enabled

○ Important for tumor suppression. 5-⑷-③)

⑵ checkpoint (checkpoint)

① Cell cycle progression must pass checkpoint

② Checkpoint : 5 items in total

③ G1 checkpoint : Point to proceed to S stage

○ Factor : Necessity of cell division, growth factor, cell size, sufficient nutrients, damaged DNA

○ Mechanism : CDK4, cyclin D

○ Stay in G0 state, which does not divide unless it passes this point

○ Example : Nerves, muscles

④ G1-S boundary

○ Mechanism : CDK2, cyclin E

⑤ S checkpoint

○ Mechanism : CDK2, cyclin A

⑥ G2 checkpoint

○ Factor : Normal DNA replication, cell size

○ Mechanism : MPF (CDK1 + Cyclin B) → promotes DNA replication

⑦ M checkpoint : Medium checkpoint

○ Factor : Microtubule attachment to all chromosomes

○ Why hybrid organisms do not reproduce

⑶ G1 checkpoint mechanism : S phase transition promotion

Example : Platelet PDGF

① 1^st. Growth factor → Ras

② 2^nd. Signaling

○ 2^nd-1^st. Ras : GDP → GTP

○ 2^nd-2^nd. GTP → Raf

○ 2^nd-3^rd. Raf → MEK

○ 2^nd-4^th. MEK → MAP kinase

○ 2^nd-5^th. MAP kinase moves inside the nucleus

③ 3^rd. Cyclin D, Cyclin E Synthesis

○ 3^rd-1^st. MAP kinase → myc

○ 3^rd-2^nd. myc → cyclin D, cyclin E gene transcription

⑷ G1 checkpoint mechanism : S-phase metastasis inhibition, p53 is mainly involved

Reference. Because G1 is the beginning of every cell cycle, there are many inhibitory mechanisms

① 1^st. UV → p53 removes mdm protein and becomes p21

② 2^nd-1^st. p21 inhibits S-phase transfer by inhibiting CDK4-cyclin D and CDK2-cyclin E (e.g., E2F Suppression)

③ 2^nd-2^nd. If cell damage is severe, p21 activates Bax → releases cytochrome C into the cytoplasm → Caspase → cell death

○ Cytochrome C : Involved in mitochondria electron transport system to be evolutionarily conserved, located in the interlumen space, attached to the inner membrane

⑸ S checkpoint mechanism

① 1^st. Increased concentrations of E2F, CDK4-cycline D and CDK2-cycline E, transcription factors

② 2^nd. Rb and E2F binding to cyclin-CDK complex inactivation

○ Rb Protein : E2F Suppression

③ 3^rd. Cyclin-CDK uses 2ATP → Rb phosphorylation

④ 4^th. Rb is phosphorylated to debond with E2F

⑤ 5^th. E2F moves to the nucleus → promotes cyclin A production

⑥ 6^th. CDK2-cycline A binding → acts as a transcription factor to complete S phase and cyclin B gene transcription

⑹ G2 checkpoint mechanism (yeast)

① 1^st. Combination of CDK1 with Cyclin B (M Cyclin) to form an inactive cyclin-CDK complex

② 2^nd. Cyclin-CDK complex is phosphorylated by WEE1 and inhibited

③ 3^rd. Phosphorylated by CDK activating kinase (CAK) to activate but not active by WEE1

④ 4^th. CDC25 Removes Phosphate Group in Cyclin-CDK Complex, Showing Cyclin-CDK Complex Activation by CAK

⑤ 5^th. Activated Cyclin-CDK Complex Activates CDC25 to Inactivate WEE1

4. Cancer

⑴ Summary

① Tumor : Inoperative cell mass made up of unregulated cell division

② Benign tumor : When tumor does not affect surrounding tissue (≠ cancer)

③ Malignant tumor : Involvement of surrounding tissues during cancer (cancer)

④ Transition : When cancer cells come out and create new tumors elsewhere (cancer)

⑤ Normal cell → Potential tumor cell (divided even without signal) → Benign tumor → Malignant tumor → Metastasis

⑵ Cancer cell characteristics

① Normal cells

○ Divide by signal, survive until needed

○ Special differentiation

○ Inability to move and invade other locations, involvement between cells and extracellular matrix

② Cancer cell

○ Genetic variation disrupts normal regulatory function, antisocial behavior

○ Step 1. Unlimited cleavage ability → benign tumor

○ Step 2. Involvement of other cell areas → metastasis

○ Metastasis to other sites through lymphatic vessels or blood vessels

○ Cancer cells can spread to 2 to 3 mm

○ Step 3. Secondary tumor formation → malignant tumor

○ Step 4. Metastatic cancer cells travel throughout the body through the circulatory or lymphatic system

③ Clinical

○ 4-5% of cancer cells are stem cells

○ It takes 5 to 10 years for cancer cells to grow to 5 mm : The younger the age of onset, the faster the rate of cancer growth

○ Normal immune function destroys up to 10 million tumor cells

○ Include at least 1 billion tumor cells when clinically detected

⑶ Type of cancer : Classification according to the organization that occurs

① Carcinoma : Epithelial tissue, high incidence, rapid proliferation and infiltration, frequent in old age

② Adenocarcinoma : Gland epithelial tissue

③ Sarcoma : Muscles and connective tissues, low incidence but not significantly affected by external factors, frequent in young age

○ Osteosarcoma (osteogenic sarcoma) : Pediatric Bone Tissue Destruction. Metastases

○ Myeloma : Disturbance of the hematopoietic action of the bone marrow, malignant tumor

○ Chondrosarcoma : Cartilage tumor

○ Sarcoma

○ Liposarcoma

④ Blood cancer

○ Leukemia : Blood tumors in which immature neutrophils multiply

○ The number of normal blood cells is so small that it is unable to carry out basic blood functions such as immune transport and oxygen transport or nutrition.

○ Immature neutrophils cause autoimmune disease and destroy normal tissue

○ lymphoma (lymphoma) : Brukitt’s lymphoma is typical

⑤ teratoma (teratoma) : Cancer where endoderm, mesoderm and ectoderm tissues are all observed

⑷ Cancer statistics

① Probability of cancer on survival to life expectancy

○ All : Life expectancy at birth (2011, National Statistical Office) 81 years old, cancer probability 36.9%

○ Man : Life expectancy (same as above) 77 years old, cancer probability 38.One%

○ Woman : Life expectancy (same as above) 84 years old, cancer probability 33.8%

② Death toll by cancer type : Man (2013)

○ Lung cancer : 12,519 people

○ Liver cancer : 8,421 people

○ Stomach cancer : 5,995 people

○ Colorectal cancer : 4,687 people

○ Pancreatic cancer : 2,615 people

○ Gallbladder and Other Biliary Cancer : 1,874 people

○ Prostate cancer : 1,629 people

○ Esophageal Cancer : 1,320 people

○ Bladder cancer : 975 people

○ Non-Hodgkin’s lymphoma : 952 people

③ Death toll by cancer type : Women (2013)

○ Lung cancer : 4,658 people

○ Colorectal cancer : 3,583 people

○ Stomach cancer : 3,185 people

○ Liver cancer : 2,984 people

○ Breast cancer : 2,231 people

○ Pancreatic cancer : 2,216 people

○ Gallbladder and Other Biliary Cancer : 1,908 people

○ Ovarian Cancer : 1,038 people

○ Cervical cancer : 892 people

○ Non-Hodgkin’s lymphoma : 657 people

④ Easy to treat cancer : Thyroid Cancer, Breast Cancer, Prostate Cancer

⑤ Hard to cure cancer : Pancreatic cancer, lung cancer, liver cancer, brain cancer

5. The occurrence of cancer

⑴ About 80 to 90% of all cancers are caused by lifestyle and environmental factors

⑵ Occurrence of mutation

① Spontaneous mutation

○ Tautomerization : Formation of bonds with other bases by isomer formation

○ Deamino Process

○ Structure by Nucleotide Type

○ Amino base : Base with only amino group (-NH₂), A, C

○ Keto base : Bases with ketone groups (C = O), T, G, U, I

○ Deamination of Cytosine (C) : Deamination of C base, change to uracil (U), change to thymine (T), finally G≡C becomes A = T

○ Deamination of Adenine (A) : Deamination of base A, change to hypoxanthine, and change to inosinic acid result in A = T finally becoming G≡C

○ Depurinization : Purine and carbon backbones are relatively weak

○ Repeat sequence (example : CAG repeats and Huntington’s disease)

○ Mistakes in the Cloning Process : The mutation rate during DNA replication of Escherichia coli and eukaryotes is similar to 1/10¹⁰ nucleotide

○ Statements that mutations are more or less frequent when comparing two populations A and B

② Induction mutation

○ DNA Modifiers

○ Nitrous acid : Induction of Deamination

○ Aflatoxin : Fungal Toxin → G-base Modified → Liver Cancer

○ Alkylating agent : Substances that donate CH3 or CH3CH2 to amino groups or keto groups of nucleotides. Ethyl methyl sulfonate (EMS) is typical

○ 2-AP (2-amino purine) : Base pair formation with thymine or cytosine

○ 5-BU (5-bromouracil) : Base pairing with thymine analogue, adenine or guanine

○ Hydroxylamine : Hydroxyl group added to cytosine, cytosine added with hydroxyl group binds to adenine

○ N-ethyl N-nitrosourea (ENU) : Random point mutation

○ Insert material

○ Acridine orange, EtBr : Flat ring molecule, insert mutation between base pairs

○ Benzopyrene : Insertion between base pair of DNA main groove → lung cancer

○ MCA (methylcholanthrene) : Chemical mutagen

○ UV irradiation : Formation of pyrimidine dimers → Deletion of mutations during replication → Skin cancer development

○ Radiation : Free radicals produced by radiation attack base or sugar-phosphate backbones

③ Transposon, retrotranspozone

⑶ DNA correction and repair

⑷ Point mutation : Gene mutation

① Base substitution mutations : Mutations due to base replacement of genes

○ Silent mutation : Even if the base is replaced by the redundancy of the genetic code, there is no difference in phenotype with the same amino acid code..

○ Missense mutation (mistake mutation) : Change to another amino acid code due to alternative base

○ Nonsense Mutations (Stop Mutations) : Loss of meaning (shortened length) due to password being changed to a stop codon

○ Neutral mutation : Change to amino acids of similar nature

○ Termination codons can be translated into significant amino acids for longer lengths

② Classification of Base Substitution Mutants

○ Transition mutations : Mutations in which purine becomes another purine, pyrimidine becomes another pyrimidine

○ Transversion mutations : Mutations in which purine is pyrimidine and pyrimidine is purine

○ Base mutations are relatively less likely to change amino acids and are more likely to return to the same site mutation.

③ Frame mutation : Mutations that shift the translation frame by base deletion or insertion of genes

④ Return mutation : Mutant individuals produce normal progeny by adding the same mutagen; almost all substitution mutations are possible

⑸ Chromosomal mutations

① Deletion

○ Deletion loop : Use for Gene Mapping

○ Near-field genes show good simultaneous deletion

② Duplication

○ Compensation loop

③ Inversion

○ Unilateral inversion (paracentric inversion) : Normal inversion 50%, non-homologous 25%, double-homologous 25%

○ Co-intrinsic inversion (pericentric inversion) : Normal 100%

④ Translocation

○ Mutual translocation : Genetic information exchange between two chromosomes, forming cross-shaped translocation

○ Holiday model

○ Example : 8 → 14

○ Emergency call : One chromosome transfers genetic information one way to another

○ Example 1. Robertsonian translocation : Causes Familial Down Syndrome

○ 1^st. Linking Jang 14 and Jang 21 : (14, 14), (21, 21) → (14, 14-21), (21, ×)

Reference. In 14-21 the isotope comes from 14, so it behaves like 14

○ 2^nd. 14 Arms and 21 Arms

○ 3rd. Germ cells : (14, 21)

(14, ×)

(14-21, 21)

(14-21, ×)

○ 4^th. Reproductive outcome with normal germ cells (14, 21)

○ (14, 14), (21, 21) : Normal, 25%

○ (14, 14), (21, ×) : Miscarriage, 25%

○ (14, 14-21), (21, 21) : Familial Down Syndrome, Unlike Normal Down Syndrome

○ (14, 14-21), (21, x) : Bleed, 25%

○ Example 2. Chronic myelogenous leukemia (CML) : Mutual translocation

○ abl gene : Encoding Tyrosine Kinase

○ bcr gene : High activity due to promoter

○ Philadelphia chromosome : Recombinant chromosome with abl and bcr genes

⑹ Chromosome nondisjunction

① Chromosome nondisjunction (nondisjunction) : Causes autosomal and sex chromosomal aneuploidy

○ Division I  nondisjunction : (n + 1, n + 1, n-1, n-1), no normal germ cells, no duplication of identical genes in germ cells

○ Division II nondisjunction : (n + 1, n-1, n, n), 50% normal germ cells, identical gene duplication in n + 1 germ cells

② Autosomal Dimerity : One or two chromosomes more or less

○ Chromosome : Loss of a pair of homologous chromosomes, prenatal implantation

○ Monosomy : Loss of 1 chromosome, lethal embryo

○ Trisomy : Embryo or Fetal Death

○ Patau syndrome (trisomy 13)

○ Edward syndrome (trisomy 18)

○ Down syndrome (trisomy 21, Down syndrome) : 1/750 births, characteristic facial structure, mental disorders, short kidneys, cardiac defects, short lifespan, vulnerability to respiratory illness, higher in maternal age

○ Haplo Ⅳ : Chromosome deletion 4 in Drosophila

③ Sex Chromosome Dimer : More or less one or two chromosomes, no significant effect, normal lifespan

○ Reason : Because the Y chromosome is less informative, only one X chromosome is active (the rest of the constituents are formed).

○ XXX (3X syndrome) : 1/1000 births, high frequency of mental disorders, phenotype normal, quasi-normal

○ XYY (2Y syndrome) : 1/2000 births, tendency to be tall, phenotype is normal, mild mental disorders, shoplifting

○ XXY (Klinefelter syndrome) : 1/2000 birth, male, tall, sexual immature, dwarf testicles, infertility, mental disorders

○ XO (Turner Syndrome) : 1/5000 birth, 99% natural abortion, dwarf, sexual incomplete maturity

④ Drainage : Mutations in which the number of chromosomes increases in multiples of n

○ autopolyploidy (autopolyploidy) : 2n (plant) individuals become 4n individuals and then breed 2n species to create 3n objects

○ Colchicine : Spindle polymerization inhibitors bind to tubulin dimers and stop cell division in the middle phase

○ Often, autopolyploidy is made using colchicine for breeding purposes.

○ Taxol : Spinach depolymerization inhibitor used as anticancer agent

○ Heteroploidy (heteroploidy, diploidy, allopolyploidy) : (Plant) individuals by breeding between nearby species

○ Mechanism of evolution

○ 1^st. Create AB object between AA and BB objects

○ 2^nd. If the AB entity is an odd chromosome, there is no fertility, so the fertility can be restored, ie AABB production

○ 3^rd. Create AABB objects that can breed between AABB and AABB objects

○ Example 1. Seedless Watermelon (3n)

○ Example 2. Triploid (3n) is 1% to 3% of total pregnancy → most of them cannot give birth and cannot survive

⑺ Cell Cycle Regulatory Genes and Cancer

① Proto-oncogenes (proto-oncogenes)

○ Genes that regulate the cell cycle often encode growth factors

○ Example 1. Growth factor or its receptor protein gene (HER2 of ovarian cancer / breast cancer)

○ Example 2. Ras (rat sarooma)

○ Activated by tyrosine kinase

○ Involved in signal transduction pathway by acting as GPCR

○ GTpase activating protein loss → Ras overactivity

○ Example 3. c-myc

○ Recombination → expression ↑ → lymphoma development on the chromosome that the c-myc gene encodes the antibody gene

○ Example 4. abl-bcr (note. 5-⑵-①)

○ Example 5. c-erbB, c-mx, c-kit, RARa, Eb, cyclin, CDK 2, 4

○ Tumor genes correspond to accelerators

○ Dominant expression : Mutation on one homologous chromosome results in mutation symptoms

② Oncogene : DNA changes due to mutations in the oncogenes

○ Mutations in tumor genes promote excessive cell division even without growth factors

○ 1^st. DNA base mutants are highly active due to structural or functional changes of the coding protein

○ 2^nd. Overexpression by amplification or rearrangement of genes

○ Example 1. Ras gene

○ Mutations in genes can lead to the development of cancer cells

○ Growth Factor Independent Cleavage

③ Tumor suppressor gene

○ Protein genes that stop cell division or repair damaged DNA at cell cycle checkpoints

○ Recessive expression : Mutation symptoms must be mutated to all homologous chromosomes

○ Example 1. BRCA2 gene

○ Located on chromosome 13, coding for a protein involved in repairing DNA damage

○ Related to Breast Cancer

○ Example 2. p53 gene : Act throughout the cell cycle,

○ p21 transcription increase

○ Associated with the expression of specific miRNAs that inhibit cell division

○ Activation of gene expression directly involved in DNA repair

○ Inhibition of Cyclin-CDK Complex on DNA Damage

○ Can induce apoptosis

○ Example 3. pRb1 : Acts on G1, inhibits E2F

○ Example 4. bcl2 : Bax Suppression

○ Example 5. APC (Note. 3-⑴)

○ Example 6. RB Protein : Substances that prevent the cell cycle from progressing

④ Multiple collision model

○ Benign tumor when the primary tumor gene is mutated to normal cells (≠ cancer)

○ Malignant tumor when tumor suppressor gene is mutated in both maternal and paternal tumors (= cancer)

○ At least 5-6 independent mutations are required in a cell : 10 ~ 20 years

⑤ Cancer outbreaks require multiple mutations

○ Benign tumors must accumulate many mutations in order to progress to cancer (∴ frequent in epithelial tissues with frequent cell division)

○ Angiogenesis : Tumors give you blood.

○ Loss of contact and anchorage dependence : Cells are layered, cancer cells can move to other locations

○ Loss of density-dependent inhibition

○ Immortalization : Telomerase activation does not limit cell division.

○ Mutations are inherited, most mutations are produced during the lifetime of the person

⑻ Immortalization Mechanisms of Cancer Cells

① Telomerace presence

② Protects telomere DNA at the end of chromosome and continues to divide more than 50 times normal cells

⑼ Colorectal cancer, colorectal cancer : One of the most cancers

① APC Tumor Suppressor Gene Defects : Polyp formation (polyp) due to excessive epithelial cell proliferation (polar, loss of contact inhibition)

○ Colorectal cancer is often found by mutations in a gene called the family adenoma polyp (APC)

○ APC Gene Mutations Are Recessive

② Ras Tumor Gene : Cell proliferation without signal, production of small benign tumors (class II adenoma, adenoma)

○ Growth factor-independent division of cancer is mostly due to Ras

③ Tumor Suppressor Gene DCC (deleted in colon cancer)

④ Tumor suppressor gene p53 deletion : Failure of G1/S identification points related to DNA damage, rapid accumulation of mutations, generation of malignancies

⑤ Deletion of the Antitransduction Gene : Metastasis, infiltration into other organs

⑥ Order is not important and cancer is generated if conditions are met

6. Cancer discovery and treatment

⑴ Discovery method

① Cancer antigen 125 (CA125)

○ Amino acid sequence of 22,000aa, also known as mucin 16 or MUC 16

○ Cellular glycoprotein of epithelial cancer with tumor antigen (CA125) recognized by monoclonal antibody, OC-125 (ovarian cancer antibody)

○ Normal value of CA 125 in serum : Less than 35U / ml

○ Therapeutic Effect of Ovarian Cancer, the Only Tumor Marker in Early Detection of Relapse

○ Prognostic Determination and Correlation with Size, Stage, and Survival of Ovarian Cancer.

○ CA125 may also increase in ovarian cancer, endometrial cancer, pancreatic cancer, lung cancer, breast cancer, colon cancer, and gastrointestinal cancer, so the screening value is low

② Biopsy : Surgically harvesting cells or tissues

○ Injection biopsy : With a needle

○ Laparoscopic : Illuminator, camera, small knife surgical tool

③ X-ray diagnostics

○ Common tumor : 108 cells

○ Palpation tumor (10 mm) : 109 cells

○ Death tumor (10 cm) : 1012 cells

⑵ How to treat

① Local tumors can be removed by surgery.

② Chemotherapy : Chemicals that kill dividing cells (cancer drugs)

○ Cocktail Therapy : Use of various cell division inhibitory chemicals

○ Resistant cells : 1/100 million. 1000 resistant cells in palpable tumors

○ Side effects of killing normally dividing cells (all cells, bone marrow, stomach wall) : Hair loss, vomiting, diarrhea

③ Radiation therapy : Use high energy radiation

○ Death of cancer cells by damaging DNA (BRCA2, p53)

○ Usually used for nearby cancer

○ Typically 10-20 radiation treatments after surgical removal of the tumor

○ Normal cells → normal cell division (by p53, DNA repair) or apoptosis

○ Tumor cell → cell death (∵ mutation increase) or malignant tumor

⑶ Cancer risk factors : Factors that increase cancer incidence

① Smoking : Tobacco contains several carcinogens, increasing free radicals, damaging DNA

② High fat, low fiber eating habits

③ Lack of exercise leads to an unhealthy immune system and an increased risk of cancer from obesity

④ Drinking : Alcohol and tobacco increase the risk with the law of multiplication

⑤ Aging : Immune system worsens, mutations accumulate

⑥ Frequent cell division

○ Recovery of damage after ovarian ovulation

○ Recovery of frictional damage from gut epithelial movement

⑦ Radioactive material, near power cable : Increased incidence of leukemia

Input : 2015.6.27 18:10

Modify : 2019.2.20 10:14