Cancer

Question 1

List the seven phenotypic hallmarks of cancer

Answer 1

1. dysregulation of cell proliferation
2. Loss of growth inhibitors
3. Mutant pro and anti-apoptotic proteins
4. Immortilzation
5. angiogenesis
6. invasion
7. genetic instability (caretaker gene

Question 2

list the three classes of genes involved in cancer

Answer 2

1. Caretaker genes ensure stability of the genome for DNA repair
2. Growth promoters
3. Growth suppressors

Question 3

Describe the different types of proteins encoded by oncogenes and their mechanism of action

Answer 3

1. Growth factors: Oncogenes cause overexpression of growth factors. Not a mutant growth factor except V sis
2. Growth factor receptors can be mutated to be constitutively active
3. Signal transduction: Ras mutation to be always active
4. Nuclear regualtory factors
5. Cell cyclin proteins

Question 4

How are oncogenes activated?

Answer 4

Mutation

chromosomal translocation–causing either placement near a powerful promoter or a hybrid protein

Question 5

Explain knudson’s hypothesis

Answer 5

Because tumor suppressor act recessively, need to knock out both WT alleles to cause cancer.

Question 6

Loss of heterozygosity

Answer 6

When cell becomes homozygous for tumor stimulating gene

Question 7

What are possible mechanisms for LOH?

Answer 7

mitotic recombination
nondisjunction
epigenetics
NOT mutation

Question 8

Describe how proteins Rb and p53 regulate cell proliferation

Answer 8

Rb regulates G1/S phase transition. Regulated by cyclin D. Causes osteosarcoma and retinoblastoma

p53: Regulates cell cycle arrest and induction of apoptosis after DNA damage. Arrests at G1/G2 phases. If dna cannot be repaired, then triggers apoptosis

Question 9

Does p53 follow the two-hit hypothesis?

Answer 9

No. Can be a dominant negative mutant allele that prevents the WT allele from functioning

Question 10

Describe how tumor cells evade apoptosis

Answer 10

1. Dysregulation of anti-apoptotic signals

2. Loss of pro-apoptotic signals

Question 11

Gatekeeper genes

Answer 11

Inhibit proliferation or cause apoptosis to maintain homeostasis in cell #

Question 12

Explain immortalization and crisis avoidance

Answer 12

Immortalization means limitless replicative potential of cells. Crisis: death of tumor cells due to chromosomal instability. Cancer cells avoid crisis by transcribing telomerase

Question 13

Describe the roll of angiogenesis in tumor formation

Answer 13

In order for tumors >1 mm, need angiogenesis. Angiogenic switch occurs when angiogenic factors exceed anti-angiogenic factors. Also helps with metastasis

Question 14

What are the steps to metastasis?

Answer 14

1. Decreased cellular adhesion w/ cadherins
2. Matrix metalloproteases
3. Integrins bind cells to ECM and regulate apoptosis
4. Angiogenesis
5. Motility and migration stimulated by growth factors and ECM matrix factors
6. extravasation
7. avoiding immune surveillance
8. survival in a new environment–certain cancers are more likely to spread to favorable environments