Cancer-Lecture 9/9/21

Question 1

Tumor supressor

Answer 1

Gene that regulates the cell cycle by preventing proliferation

Question 2

Telomeres and telomerase

Answer 2

Telomeres are protective ends of DNA, telomerase maintains them, needs to be reactivated in cancers

Question 3

Oncogenes

Answer 3

Activated protocol-oncogenes, usually signal molecules telling the cell to proliferate

Question 4

Proto-oncogenes

Answer 4

Oncogenes that have not acquires a mutation to be activated yet

Question 5

Retinoblastoma

Answer 5

A rare cancer that happens in children that acquire a defective RB allele. Only need one more to mutate to cause disease

Question 6

E2F

Answer 6

Inhibited by RB, it is a transcription factor that promotes the expression of genes needed for S phase

Question 7

Mechanism of action of pRB

Answer 7

Active RB is unphosphorylated, inhibits E2F. RB is inactivated by phosphorylation by CDK which allows E2F to exert its effects and initiate DNA replication

Question 8

P53

Answer 8

Tumor suppressor that regulates cell cycle and apoptosis, phosphorylated in times of stress

Question 9

p53 mechanism of action

Answer 9

Phosphorylated under conditions of stress which stabilizes, acts as a transcription factor for p21, which binds to both Cdk/cyclin complexes and PCNA to inhibit cell cycle

Question 10

p21

Answer 10

Protein that is unregulated by p53, binds to both PCNA and Cdk/cyclin complex to stop cell cycle

Question 11

Examples of tumor suppressors (6)

Answer 11

RB
P53
NF1 (neuroblastoma)
APC (Colon, stomach)
BRCA 1 (breast cancer)

Question 12

Alterations to signal transduction cascade linked to cancers (4)

Answer 12

1. Excess growt factor
2. Defective growth factor receptors
3. Defective signaling molecules
4. Altered regulation of transcription factors

Question 13

Simian sarcoma (sis) oncogene

Answer 13

Gene encodes part of the PDGF molecule and is able to induce signal transduction when there’s no signal there

Question 14

HER2/ErbB

Answer 14

Examples of altered growth factor receptor, can stimulate growth without Epidermal growth factor (EGF)

Question 15

Ras

Answer 15

Important molecule in signal transduction, active when bound to GTP and is inactive when bound to GDP. Can hydrolysis GTP to turn off with help from GAPs

Question 16

Ras oncogene

Answer 16

Lost intrinsic GTPase activity, therefore always bound to GTP and always telling the cell to grow and divide

Question 17

Overexpression of c-fos and c-jun

Answer 17

Cancer cells overexpress these two transcription factors

Question 18

Myc proto-oncogene

Answer 18

Regulates the expression of ~15% of all genes, binds to enhancer sequences. Mutated Myc are found in many cancers, up-regulation of many genes, some involve cell proliferation

Question 19

Burkitt’s Lymphoma

Answer 19

Involves a translocation of chromosome 8, when translocated, Myc is constitutively expressed

Question 20

T-antigen

Answer 20

SV40 vital infection, sequesters both Rb and p53, which causes the cell to proliferate

Question 21

Transformation by HPV

Answer 21

E6 creates protein binding p53 and E7 transcribes a gene sequestering pRB, causes cancer

Question 22

E6

Answer 22

HPV gene coding for protein capable of binding p53 and targeting it for proteolytic

Question 23

E7

Answer 23

Codes for a gene capable of binding pRB

Question 24

Acquired capabilities of cancer (6)

Answer 24

Evading apoptosis
Self sufficiency in growth signals
Insensitivity to anti growth signals
Tissue invasion and metastasis
Limitless replication (telomerase activation)
Sustained angiogenesis