Cancer And Cell Cycle

Question 1

Hallmarks of cancer

Answer 1

1. Self sufficiency of growth signals (oncoenes)
2. Insensitivity to antigrowth signals (RB gene)
3. Evasion of apoptosis (p53)
4. Limitless replicative potential (telomerase)
5. Sustained angiogenesis
6. Tissue invasion and metastasis
   - absent fibronectin: decreased cell adhesion, increased motility, production of proteases that degrade basal lamina

Question 2

Crucial enabling trait

Answer 2

Genetic instability: must disrupt p53 pathway

Question 3

Carcinogens

Answer 3

Chemicals known to cause cancers

Many substances are precarcinogens and activated by cytochrome p450 in the liver

Cause crosslinks, chemical links, hydroxylate, or break DNA

Question 4

Oncogenes

Answer 4

Precancerous genes

1. Point mutation, most frequently a RAS oncogene
2. Gene amplification
3. Chromosomal translocation (22 and 9)
4. Local DNA rearrangements

Question 5

Cell Cycle

Answer 5

G1/s: cdk-cyclin phosphorylates Rb protein to bind E2F, prevents S phase… cancer (HPV) blocks Rb function using E7, can’t maintain checkpoint

G2/M: Mad and Bub proteins check mitotic spindle

Question 6

P53

Answer 6

P53 is a tumor supressor gene, mutated in half of all cancers
Supposed to check for DNA damage, if broken it activates ATM protein kinase and p21, halts cell cycle for repair
If can’t be repaired, triggers apoptosis

1. P53 disruption causes failure of apoptosis
2. P53 is targeted by cancer viruses

Question 7

Apoptosis

Answer 7

Triggered by death signals or release of cytochrome c from mitochondria

Cytotoxic T lymphocytes recruit procaspase 8 to kill infected cells
Bad protein is pro-apoptotic, other anti-apoptotic proteins withdraw

Question 8

Tumors

Answer 8

Initiation, promotion, progression