chapter 20 ; cancer; overview, proto-oncs, TSG

Question 1

describe a benign tumor

Answer 1

still responds to cell signaling properly, not deadly, but can be fatal in the brain

Question 2

describe a malignant tumor

Answer 2

loss of cell adhesion and communication, can invade and disrupt tissues

Question 3

what type of proteins cause cells to leave area and metastasize if they are mutated?

Answer 3

cohesion proteins

Question 4

old belief of cancer

Answer 4

it was believed that humans lost genes due to a mutation, which allowed fast unregulated growth, lost adhesion, and signal recognition
* rare event that a cell had such mutations and accumulated over time

Question 5

actual occurrence of cancer

Answer 5

• a cell loses ability to complete regulated growth, cell adhesion and recognition
  -immune system misses the cell and it continues to reproduce.

Question 6

give an overview of b cells working in the immune system

Answer 6

• the immune system can recognize cancer cells
• b cells are made in the bone marrow and is exposed to all proteins made in the body, has the chance to stick, the combination makes a dead b cell.
• b cells that don’t stick are released to the body this eliminates cells that stick to our own proteins.

Question 7

cells have TSA’s and TAA’s, describe them

Answer 7

TSA: tumor specific antigen. proteins produced on a cancer cell that other cells do not have. due to fetal development genes. b cells are unfamiliar and bind to them
TAA: tumor-associated antigen, proteins that can be recognized, associated at an elevated level.

Question 8

the cell cycle has ________, that trigger progression into the next phase, turns on genes

Answer 8

CDK- cyclin complexes, checkpoints

Question 9

Cyclin

Answer 9

proteins made in large numbers and are quickly degraded

Question 10

CDK

Answer 10

cyclin dependent kinases, an enzyme

Question 11

Cyclin-CDK

Answer 11

: complexes, phosphorylate proteins

Question 12

G1 Cyclin CDK

Answer 12

activates and turn on genes that make ligase, polymerase, etc

Question 13

in cancer cells which phases of the cell cycle are short and effect proto-oncogenes and tumor suppressor genes?

Answer 13

Phases G1 and G2

Question 14

cancer traits

Answer 14

• some cancers are hereditary: 10%
• sporadic cancer: not inherited, more common, start from ones own cell. 90%
• some viruses can induce cancer: called retrovirus. start as RNA revert back to DNA and inserted into chromosome. they tend to have lytic and latent phase. if they dont have a latent phase they tend to kill the cell they are in which does not cause cancer
  -descendants of cancerous cells are all cancerous, don’t revert back
  -can increase the risk of cancer through exposure of mutagens, mutation rate is increased. mutations drive cancer
  -certain chromosomal mutations are associated with particular forms of cancer. chromosome 17 has BRACA-2 and chromosome 13 has BRACA 1

Question 15

healthy cells vs tumor cells

Answer 15

healthy cells: need factors that stimulate and also prevent growth
tumor cells: dont regulate, shorten G1 and G2.
-lose genes to a mutation, not cancerous yet
-replicates and mass-produces
-as a tumor gets larger it has a lot of cells that lost function and further accumulate more mutations
-more mutations cause a higher risk of cancer.

Question 16

what are the types of cancer genes?

Answer 16

-proto-oncogenes to oncogenes
-tumor suppressor genes
-miRNA genes
-mutator genes

Question 17

briefly describe proto-oncogenes

Answer 17

proteins produced by these genes move the cell cycle forward, function normally. can be modified into oncogens, they function in a dominant way, only a single copy of the gene can lead to an imbalance in cell regulation
-ex. RAS, Src, C-oncs, V-oncs
-RAS: g coupling protein
-Src: tyrosine kinase
-C-oncs: chromosomal: Src, RAS, CDKs
-V-onc: viral genes that move cell cycle forward

Question 18

describe oncogenes

Answer 18

mutated proto oncogene, functions without regulation too well, more active than normal or at inappropriate times. function in a dominant manner, only need 1 gene to increase risk.

Question 19

briefly describe tumor suppressor genes

Answer 19

proteins produced by the gene promote slowed or paused cell cycles
ex. p53, p14, pRB
-mutations act in a recessive fashion, both mom and dads need to be mutated

Question 20

briefly describe miRNA gene

Answer 20

play an important role in RISC formation and can act as either proto-oncogenes or tumor suppressor genes
ex. Let-7 miRNA and mi373/372

Question 21

briefly describe mutator genes

Answer 21

proteins produced by these genes repair damaged DNA. with such repairs all the other cancer genes have a greater chance of not functioning properly.
-includes BRACA 1 and 2, UvR system, mutation repair exam 2 material.
-act more as TSG; revert DNA to normal state
-if you lose ability to fix genes, you begin to accumulate more mutations, more likely to damage proto-oncs and TSGs
-when they work properly they help prevent cancer
-both need to be broken to cause issues

Question 22

describe the proto-oncogene signal transduction pathway

Answer 22

*overall involves positive control of cell growth, products that stimulate growth or are present in the pathway
-stimulus and binding of a hormone to receptor activates SRC
-Src: membrane associated non-receptor protein tyrosine kinase, kinase can phosphorylate other proteins, quickly interacts with g coupling protein RAS
-RAS: g coupling protein, once activated converts GTP to GDP, then activates adenyl cyclase, need high levels
-Adenylyl Cyclase: enzyme, converts ATP to cyclic AMP.
-cAMP: interacts with protein kinase A, dislodge and phosphorylates protein kinase A
-protein kinase A: becomes activated, enters nucleus and phosphorylates activator proteins
-activator proteins: turn on gene for cyclins
-cyclins: build up and bind to CDK’s
-CDK: once activated, phosphorylate pRB
-pRB: regulates at G1-S. found with E2F

Question 23

Tumor suppressor genes: Retinoblastoma

Answer 23

-type of cancer, takes two mutated gene, helps understand sporadic and hereditary cancers
-hereditary: mutation, inherit from mom and a bad mutated version. sperm hits egg, that particular cell has a bad and good version of gene, leads to every cell inheriting the bad version.mutation is present in 70 trillion cells, any one cell gets 2nd mutation which makes it cancerous
-sporadic: 90%, many cells lead to a large chance of one type cancer to come up. after you are born you get the same mutation, every cell has the mutation. need to hit the same cell for it to become cancerous

Question 24

describe pRB and its interactions with E2F:

Answer 24

pRB: protein retinoblastoma , involved at G1-s checkpoint, found in complex with E2F
-unphosphorylated: inhibits transcription factor E2F, functions as TSG= slows
-phosphorylated: inhibition of E2F is removed and the transcription factor turns on transcription for DNA synthesis.
-E2F: activator for proteins that copy DNA (helicase, ligase), cell cycle moves forward S phase.

Question 25

inheritance of E2F

Answer 25

if there is a mutation in one, you have one nonfucntional E2F, the other still moves the cycle forward. if one can still bind and interact with pRB but cannot interact: it is oncogenic.

Question 26

pRB mutation: TSG; inheritance

Answer 26

if it is mutated=broken protein but still have good protein made from the other. need both to be mutated to lose control

Question 27

what is p53

Answer 27

transcription factor that is regulated by phosphorylation. T-factor for WAF-1 and DNA repair genes.
-triggers a cascade when phosphorylated to repair DNA
-can bind to enhancer regions with activators, help accumulate and stabilize transcriptions of WAF-1 genes

Question 28

what is the function of mdm

Answer 28

degrades p53 to appropriate levels.
-when it is phosphorylated there is no p53 mdm complex, no degradation of p53 and it accumulates

Question 29

what triggers the phosphorylation of p53 and mdm?

Answer 29

• damage from a cell from thymine dimers, base analogs, base modifying agents, the single stranded damage is recognized by components of cells.

Question 30

describe cascade 1 in the p53 TSG

Answer 30

-p53 sticks and helps promote transcription of WAF1 gene
-WAF1: codes for p21
-p21: binds to CDK that are bound to cyclins=inactivates. ex. cannot phosphorylate pRB
-if pRB is not phosphorylated it remains attached to E2F and inhibits
-E2F: will not be able to function as an activator for S phase proteins
-Pause: allows nucleotide base excision to occur
-if it works: back to normal DNA, and mdm and p53 will accumulate and interact unphosphorylated. cycle continues

Question 31

what happens if the cascade 1 does not repair the DNA effectively?

Answer 31

unphosphorylated p53 levels rise and binds to promiscuous repair mechanism

Question 32

describe cascade 2 in the p53 TSG

Answer 32

-turns on a new polymerase to repair mutations and damage
-allows a new base to come in, but does not function as accurate
-if it doesnt function well: p53 accumulates to high levels and binds to another enhancer region

Question 33

describe why p53 can bind to enhancer regions and trigger cascades easily

Answer 33

-phosphorylated sticks better, the more you have the time it spends to stick.

Question 34

describe cascade 3 in p53 TSG

Answer 34

-needs a high amount of p53 to bind or else it will fall off
-binds to BAX enhancer region
-BAX gene: males BAX protein , accumulated over time. Binds to BCL-2.
-BCL-2: if present in high numbers with no BAX it makes a BCL-2 complex
-BCL-2 complex: inhibits mitochondrial permeability=prevents apoptosis
-as complex increase, BAX anneal and stimulate mitochondiral permeability=release citochrome c
-citochrome c: binds to other proteins, activators for caspase
-caspase: triggers apoptosis

Question 35

do healthy cells produce BAX?

Answer 35

no they don’t need to, apoptosis is not needed

Question 36

what is p14?

Answer 36

-protein identified in some cancers
-ARF: alternative reading frame gene, helps stabilize p53
-need to lose both if it fails

Question 37

BRACA-1 and BRACA-2

Answer 37

breast cancer associatedd can act like mutator genes which are TSG. both terms are used because they play a role in suppressing tumors by repairing double strand breaks

Question 38

describe BRACA-1:

Answer 38

involved in cellular responses to DNA genes, transcription genes, transcription regulation and the addition of ubiquitin to proteins
-functional: keeps a region on a heterochromatin near the centromere tightly packaged
-broken: is unpackaged and unstable: causes more chances for complete breaks
mutations cause: cause transcription of silenced heterochromatic regions of chromosomes. this causes global chromosome instability and disruption of normal cell cycle checkpoints. uncontrolled proliferation ensues

Question 39

describe BRACA-2:

Answer 39

encodes a protein that interacts with RAD-51. both work to repair break using the second chromosome.
nonfunctional: breaks accumulate and missing pieces on chromosomes, mutations arise
-if a bad version is inherited, more likely to have caner.

Question 40

RAD 51

Answer 40

binds to ss DNA, repairs. interacts with BRACA-2

Question 41

________ unphosphorylated interacts with mdm and is degraded

Answer 41

p53

Question 42

nonfunctional p53 causes

Answer 42

no pause in the cell cycle when there is DNA damage, mutations accumulate, cause cancer, mutations make proto-oncogenes too functional and knock out TSG, cells font die, mistakes accumulate