Tumor Supressors And Oncogenes

Question 1

What are tumor suppressors

Answer 1

The brakes on the cell that are lost during cancerous progression

They encode protiens that:

suppress the formation of a tumor

Suppress cell motility

Repair dna damage

Limit cell proliferation

Question 2

What are protooncogenes

Answer 2

The accelerators of cell proliferation in the cell and are activated during cancerous progression

They encode protiens that promote the loss of growth control

They do normal regulation but when mutated become oncogenes that are cancerous

Question 3

What are examples of tumor suprressors

Answer 3

1. Transcription factors (p53)
2. Cell cycle regulators (pRB)
3. Regulators of signalling pathways
4. DNA repair protiens (BRCA1 and 2)
5. Phosphoinositide phosphatase
6. Cell junction protiens: E- Cadherins (prevent migration)

Question 4

How does retinoblastoma happen

Answer 4

Both copies of the RB gene must be inactivated for cancer to arise

There are spontaneous and hereditary cases

Question 5

What is the spontaneous case of retinoblastoma

Answer 5

They have two normal copies of the RB gene

One copy spontaneously mutates, then another spontaneously mutates. Then RB cancer occurs

The likelihood of both alleles getting mutations in the same somatic cell is low

Question 6

What is the hereditary case of retinoblastoma

Answer 6

Every cell has an inherited mutation in one copy of the allele

Then only one spontanous mutation would need to happen in any cell for RB cancer to occur

The chance of a second mutation in any cell is high

Question 7

What needs to happen to a tumor suppressor in order for cancer to occur

Answer 7

Both copies of the tumor suppressor gene need to be mutated/ inactive

Question 8

How does pRB act as a tumor suppressor

Answer 8

It holds back the G1-S cell cycle by binding to E2F

Question 9

How does the tumor suppressor p53 function

Answer 9

If dna damage occurs in a cell, the p53 levels rise and p53 gets phosphorylated by CHK2

P53 acts as a transcription factor to make the p21 gene.

The p21 CDKI bind to the CDK and causes cell cycle arrest at g1.

But if dna can’t be repaired p53 enhances the expression of a gene the encodes a cell death protien that does apoptosis

If no p53, then tumor occurs since cell cycle didn’t start

Question 10

What is p21

Answer 10

A cyclin dependent kinase inhibitor

Question 11

What do chemotherapeutic drugs do

Answer 11

They induce dna breaks to kill cells that are rapidly dividing

Do apoptosis of cells

Question 12

What happens to cells without p53 when there’s is chemotherapeutic drugs

Answer 12

With p53 they would do apoptosis and die

But without p53 they still survive

Question 13

Explain the effect of diff levels of p53 on apoptosis due to chemotherapeutic drugs

Answer 13

When both copies of p53 are present, the cells are most sensitive to the drug and die

When one copy is mutated, the cells are not as sensitive to the drug and less die

When both copies mutated, the drugs have no effect and all cells survive

Question 14

What are oncogenes

Answer 14

They are abnormally expressed/mutated forms of proto oncogenes that promote the loss of growth control

Abnormal regulation

Question 15

How does progression of a tumor from protooncogenes differ from tumor suppressor

Answer 15

The protooncogenes need only one mutated alleles to become an oncogene and cause abnormal cell growth leading to a tumor (the mutation is dominant at the cellular level so only one copy is needed)

The tumor suppressors need mutations in both alleles for loss of growth control (recessive mutation at the cellular level)

Question 16

How does a protooncogenes become activated to an oncogene

Answer 16

Mutation or deletion

Gene duplication

Translocation

Question 17

Describe a Mutation or deletion of a protooncogene that turns it into an oncogene

Answer 17

The protooncogene gets a point mutation that affect its genes function

The resulting protein has changed structure and function

Question 18

Describe how gene duplication of a protooncogene turns it into an oncogene

Answer 18

If the protooncogene is duplicated it encodes and produced too many protiens

If too many activation protiens, it’s cancerous

Question 19

Describe how translocation of a protooncogene turns it into an oncogene

Answer 19

2 ways:

1. A regulatory dna sequence from a diff gene get attached to the protooncogene

This increases expression of the down steam protooncogene and make more resulting protiens

2. A protien coding region of a diff gene fuses with the protooncogene. This make a fusion gene which makes a fusion protien

The fusion protien is not under normal control

Question 20

What types of protiens are encoded by protooncogenes

Answer 20

1. Growth factors and receptors (EGFR)
2. Protein kinases or protien that activate protein kinases (SRC, FYN, RAS)
3. Cell cycle control protiens (cyclin D)
4. Proteins that regulate apoptosis
5. Transcription factors (CDK, Fos, Jun)

Question 21

What is ErbB2/HER2

Answer 21

It’s a receptor that is related to EGFR

It’s targeted by a drug called herceptin in breast cancer

Activate the MAPK pathway

Question 22

What do SRC FAK AND RAS do

Answer 22

Protooncogenes That activate the MAPK pathway to promote Adhesion dependent cell proliferation and survival

A mutation in one of these could allow the cancer cell to survive without adhering to the ECM