2-14 thru 2-19

Question 1

What is the genetics name for the short arm of the chromosome? The long arm?

Answer 1

p arm, the long arm is called the q arm

Question 2

What is the difference between an oncogene and a tumor suppressor gene?

Answer 2

oncogenes= growth promoters, tumor suppressors = growth suppressors

Question 3

What are the three functions of proto-oncogenes (when mutated, they become oncogenes)

Answer 3

promote cell division, differentiation, and stop cell death

Question 4

What class of proteins are usually made from proto-oncogenes?

Answer 4

kinases

Question 5

Why did scientists first believe that oncogenes were contagious

Answer 5

Src in rooster was the first identified oncogene, and it was known to originate from viral-induced mutation

Question 6

By what 3 WAYS are proto-oncogenes activated

Answer 6

1. one mutation needed to make hyper-activated as a gain-of-function mutation 2. gene is duplicated/ amplified and expression mevel is increased 3. gene is translocated to fuse with another gene, making it basally active

Question 7

What kind of molecules are growth factor receptors?

Answer 7

receptor tyrosine kinases- dimerize to transphosphorylate

Question 8

In what 3 WAYS are receptor tyrosine kinases made constitutively activated?

Answer 8

1. affinity for transphosphorylating region increased 2. loss of extracellular control domain 3. overactive autocrine signalling

Question 9

What are 2 commonly mutated growth factor proto-oncogenes

Answer 9

EGFR & HER2 (A.K.A. ERBB1 & 2)

Question 10

What kind of mutation if HER2 known for?

Answer 10

gene amplification

Question 11

What are the 3 proteins immediately downstream of ERBB receptors?

Answer 11

Ras, P13K, Raf

Question 12

How does Ras function normally vs. when mutated to an oncogene

Answer 12

Ras is a GTPase that turns off when in GDP-bound form. When transformed into an oncogene, it does not care if GTP or GDP is bound- it is always active

Question 13

What is the product of PIK3CA and what role does it play in cancer?

Answer 13

product= the catalytic residue of phosphotidylinositide-3-kinase (PI3K), a protein regulated by Ras or directly by growth factor receptors. When made constitutively active, it phosphorylates the 3’ Carbon of PIP3, signalling for cell growth

Question 14

How does Adk relate to the ERBB pathway?

Answer 14

ERBB stimulates Ras, stimulates PI3K, stimulates PIP3, stimulates PH -> binds PDK1/Adk, PDK1 activates Adk

Question 15

What is the difference between oncogene mutations and tumor suppressor mutations?

Answer 15

Oncogenes get gain-of-function mutations, tumor suppressors get loss-of-function mutations. Oncogenes get DOMINANT mutations, and tumor suppressors are recessive

Question 16

What theory of tumor suppressor development was derived from the first tumor suppressor gene, Rb1

Answer 16

The two-hit hypothesis (one bad copy gives rise to cells that may develop “2nd hit” in the same cell or its progeny)

Question 17

What is LOH? What does it refer to?

Answer 17

Loss-of-heterozygosity: referring to the 2-hit mechanism of tumor-suppresor derived cancer mutations

Question 18

What are the 4 FUNCTIOS of tumor suppressors

Answer 18

1. cell cycle check points 2. inhibition or regulation of cell cycle 3. promote apoptosis 4. participate in DNA repair

Question 19

What is the R-point

Answer 19

restriction point in G1. when the cell receives signal from environment that its ok to replicate and makes a nearly ABSOLUTE commitment to replicate

Question 20

What is the function of Rb

Answer 20

Rb gets phosphorylated by cyclin D/Cdk 4/6 complex. This inactivates Rb so it can’t block the TF that allows progression through cell cycle

Question 21

How does normal functioning p16 prevent the cell from progressing through the cell cycle

Answer 21

prevents cyclin D from interacting with Cdk4/6

Question 22

Name the ways the cell can bypass the R-point in cancer

Answer 22

By upregulating Cyclin D1 or Cdk 4/6 or Cyclin E or Cdk2 or making Rb more prone to hyperphosphorylation or blocking it from blocking the TF for commitment to cell cycle

Question 23

what is the most frequently mutated gene of all cancers?

Answer 23

p 53 - it does EVERYTHING, determines if halted cell cycle should be repaired or trigger apoptosis

Question 24

Why does The structures of p53 make it possible to give a dominant negative mutation if one allele is ‘hit’

Answer 24

It is a homotetramer TF

Question 25

How is conc. of p53 regulated?

Answer 25

It is auto regulated by MCM2, stress blocks degradation of p53

Question 26

What kind of mutation in p53 causes cancer

Answer 26

Decrease the activity of p53 so concentration of MCM2 is Kept low and concentration of p53 increases

Question 27

What is PTEN’s normal function in the cell

Answer 27

Prevents PIP3 from being over-activated (phosphorylated), thus suspressing growth and survival signals of the PI3K pathway

Question 28

Why is PTEN a weird enzyme

Answer 28

It is a lipid phosphotase rather than a protein phosphotase

Question 29

How is PTEN deregulated in cancer

Answer 29

It is made less active or expressed at lower levels

Question 30

What class of proteins are BRCA1, 2? are they related?

Answer 30

nuclear proteins that act in DNA repair (HDR). Not related

Question 31

What is the effect of dysregulating BRCA1, 2? Is it usually a dominant or recessive mutation?

Answer 31

Dysregulating BRCA1 or 2 causes genome instability, ANEUPLOIDY, increasing the likelihood of mutation. It is a recessive mutation.

Question 32

What 3 genes are mutated to cause loss of ability to senesce?

Answer 32

Rb1, p53, telomerase

Question 33

Why do chr arms shorten?

Answer 33

RNA polymerase needs space to make the primer for replication

Question 34

Is APC a tumor suppressor or an oncogene

Answer 34

tumor suppressor (LOH mutation needed)

Question 35

What are the energetic differences of a resting cell versus and actively proliferating cell?

Answer 35

Metabolism is increased, as seen in an increase in cellular concentrations of glucose, glutamine, and lipids. Increased glycolytic rate means that cells are in a more acidic environment when cancerous

Question 36

How is increased glycolysis detected in cancer?

Answer 36

Use of F-18-deoxyglucose and visualizing rate of uptake by PET scan

Question 37

Warburg Effect

Answer 37

Increased uptake of glucose in cancer cells

Question 38

Why do cancer cells display a high level of aerobic glycolysis?

Answer 38

They adapt from a hypoxic environment before angiogenesis phase

Question 39

What metabolic adaptation allows tumor cells to become invasive

Answer 39

ability to thrive in acidic environment

Question 40

Which class of cancer genes directly increases the ability of the cell to upregulate intake of metabolites

Answer 40

oncogenes (like EGFR, PI3K, PTEN, etc.)

Question 41

hTERT definition, and what class of cancer gene

Answer 41

telomerase. oncogene.