HMB265H1 Lecture : Lecture 23- Genetics of Cancer

For your responses please justify your answer. No justificationfor answer will recieve "needs work" rating.

Multiple choice. Circle all that apply.
49. Which of the following statements concerning cancer cells arecorrect?
A) The ability of cancer cells to cross the basal lamina is arelatively unimportant factor in
determining whether they will metastasize to form secondarytumors.
B) Cancer cells gradually accumulate a variety of mutations thatcause them to progressively
become less responsive to the external signals that normallycontrol cell growth.
C) Over half of human tumor cells exhibit mutations in the p53gene.
D) The proliferation of cancer cells is sensitive to compounds thatblock microtubule
depolymerization.
E) Cancer cells generally retain normal cell cycle checkpointfunctions.

True or False. For either response, please justify youranswer.

50. True/False One possible function of a tumor suppressor geneis to control a cell cycle
checkpoint.

Her2 is an EGF receptor family member that drives proliferation of cells including in the breast. Too much Her2 signaling can contribute to Her2 positive breast cancer. Mutations can be generated in different proteins in the Her2 signaling pathway. The following are 5 different possible mutations.

Mutant a: Ras protein that cannot exchange GDP for GTP.

Mutant b: RAF protein with a mutation in the active site such that ATP does not bind.

Mutant c: Her2 receptor that lacks tyrosines in its intracellular domain.

Mutant d: MAPK that is constitutively active.

Mutant e: Myc expressed 10X higher than normal.

The following cell lines with mutations in Her2, Ras/MAPK pathway are treated with the ligand for the Her2 receptor and compared to normal cells treated with ligand. For each Her2 mutant pathway cell line, describe whether myc synthesis is higher or lower compared to normal cells and if proliferation (cell division) is higher or lower compared to normal cells treated with ligand

A. Cell line with mutations a and b.

B. Cell line with mutations c and e

C. Cell line with mutations d and e

D. Rb is also important for regulation of the cell cycle at the restriction point or start. What would be the effect on myc and cell proliferation of a mutation that switched all the serines and threonines that are phosphorylated to alanine?

Tumor cells often develop mutations that lead to the loss of mitochondria. However, tumor cells are still able to proliferate rapidly even in the presence of oxygen. (1) How is this possible? (2) How would a drug that inhibits hexokinase interfere with cancer growth? (3) Give 2 examples of how a drug could inhibit hexokinase. (4) How could normal cells survive?