Viruses & Cancer

Question 2

What is the role of Cyclins/Cdks?

Answer 2

Regulate progression through stages of proliferation

Question 3

What causes cancer?

Answer 3

Mutations that turn a regular cell into a transformed cell – pile up, don’t require anchoring, unlimited proliferation, unstable genome

Question 4

tumor suppressor

Answer 4

inhibits cell cycle progression; cancer mutation = loss of function (must lose both copies)

Question 5

proto-oncogene

Answer 5

stimulates cell cycle progression; cancer mutation = gain of function (only need to mutate one copy)

Question 6

examples of tumor suppressors

Answer 6

Rb, p53, p16, ARF

Question 7

examples of proto-oncogenes

Answer 7

cyclin D1, Mdm2, myc, ras

Question 8

Cyclin D-Rb Pathway

Answer 8

Cyclin D (PO) binds to Cdk4/6, leads to inhibition of Rb (TS) so that it no longer inhibits E2F transcription of S phase genes

Question 9

p53-p21-Cyclin Pathway

Answer 9

p53 promotes p21 which inhibits Cyclin/Cdk, but Mdm binds p53 and prevents it from regulating p21 (ARF suppresses Mdm)

Question 10

How does one get cervical cancer from HPV?

Answer 10

HPV DNA integrates into tumor cell DNA – E6/E7 genes in the HPV genome induce cell cycle progression and thus can be transforming in human cells

Question 11

What does E6 target?

Answer 11

Rb tumor suppressor

Question 12

What does E7 target?

Answer 12

p53 tumor suppressor

Question 13

EBV and KSHV promote what types of cancer?

Answer 13

lymphoid and epithelial; express genes during latency that promote cell growth and suppress apoptosis

Question 14

What are the major oncogenes in EBV?

Answer 14

LMP1, LMP2A

Question 15

What is LMP1?

Answer 15

integral membrane protein acts as constitutively active CD40 receptor that activates multiple pro-survival pathways

Question 16

What is EBNA1?

Answer 16

EBV protein that maintains viral episome within proliferating cell population by tethering it to the host chromosome

Question 17

What type of cancer is associated with chronic hepatitis?

Answer 17

primary hepatocellular carcinoma

Question 18

How does HCV lead to carcinoma?

Answer 18

persistent lytic replication results in inflammation, cell death, which induces proliferation to replace the lost cells –> self-induced tumorigenesis

Question 19

what is the relationship between chronic inflammation and cancer?

Answer 19

activated inflammatory cells lead to ROS, RNS, cytokines which cause DNA damage (genome instability) and tissue damage (cell turnover). Together = tumor initiation and progression

Question 20

H. pylori and peptic ulcer disease are associated with what type of cancer?

Answer 20

non-cardia gastric cancer

Question 21

DNA damage leads to?

Answer 21

more mutations.

Question 22

Cell turnover leads to?

Answer 22

more mutations.