Tumor Supressors And Oncogenes Flashcards
What are tumor suppressors
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
What are protooncogenes
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
What are examples of tumor suprressors
- Transcription factors (p53)
- Cell cycle regulators (pRB)
- Regulators of signalling pathways
- DNA repair protiens (BRCA1 and 2)
- Phosphoinositide phosphatase
- Cell junction protiens: E- Cadherins (prevent migration)
How does retinoblastoma happen
Both copies of the RB gene must be inactivated for cancer to arise
There are spontaneous and hereditary cases
What is the spontaneous case of retinoblastoma
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
What is the hereditary case of retinoblastoma
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
What needs to happen to a tumor suppressor in order for cancer to occur
Both copies of the tumor suppressor gene need to be mutated/ inactive
How does pRB act as a tumor suppressor
It holds back the G1-S cell cycle by binding to E2F
How does the tumor suppressor p53 function
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
What is p21
A cyclin dependent kinase inhibitor
What do chemotherapeutic drugs do
They induce dna breaks to kill cells that are rapidly dividing
Do apoptosis of cells
What happens to cells without p53 when there’s is chemotherapeutic drugs
With p53 they would do apoptosis and die
But without p53 they still survive
Explain the effect of diff levels of p53 on apoptosis due to chemotherapeutic drugs
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
What are oncogenes
They are abnormally expressed/mutated forms of proto oncogenes that promote the loss of growth control
Abnormal regulation
How does progression of a tumor from protooncogenes differ from tumor suppressor
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)
How does a protooncogenes become activated to an oncogene
Mutation or deletion
Gene duplication
Translocation
Describe a Mutation or deletion of a protooncogene that turns it into an oncogene
The protooncogene gets a point mutation that affect its genes function
The resulting protein has changed structure and function
Describe how gene duplication of a protooncogene turns it into an oncogene
If the protooncogene is duplicated it encodes and produced too many protiens
If too many activation protiens, it’s cancerous
Describe how translocation of a protooncogene turns it into an oncogene
2 ways:
- 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
- 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
What types of protiens are encoded by protooncogenes
- Growth factors and receptors (EGFR)
- Protein kinases or protien that activate protein kinases (SRC, FYN, RAS)
- Cell cycle control protiens (cyclin D)
- Proteins that regulate apoptosis
- Transcription factors (CDK, Fos, Jun)
What is ErbB2/HER2
It’s a receptor that is related to EGFR
It’s targeted by a drug called herceptin in breast cancer
Activate the MAPK pathway
What do SRC FAK AND RAS do
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
