Lecture 4: Carcinogenesis

Question 1

What are initiators?

Answer 1

Mutagens that hit oncogenes and tumor suppressors

Question 2

What are promoters?

Answer 2

Substances that drive proliferation without causing oncogene or tumor suppressor mutations themselves.

Question 3

True or false: Enough hits by promoters can cause mutations without a hit by an initiator.

Answer 3

False; Cells must first be hit with mutations by a tumor initiator to generate cancer.

Question 4

True or false: If a cell is hit first by a promoter, then by an initiator, cancer will result.

Answer 4

False; initiators must hit first.

Question 5

True or false: Tumor promoters increase the proliferation of cells with pre-existing mutations without themselves being mutagenic.

Answer 5

True

Question 6

Mutagens that hit oncogenes and tumor suppressors

Answer 6

Initiators

Question 7

Substances that drive proliferation without causing oncogene or tumor suppressor mutations themselves.

Answer 7

Promoters

Question 8

What is the general progression of hits in colorectal cancer?

Answer 8

1) Inactivation of the tumor suppressor APC
2) Activation of the oncogene Ras (KRas)
3) Inactivation of SMAD2/SMAD4 tumor suppressors
4) Inactivation of p53
5) Other mutations that increase the selective advantage of these mutated cells.

Question 9

What are the four characteristics of epithelial cells that are disrupted during the formation of an epithelial carcinoma?

Answer 9

1) They line the insides of organs and provide a barrier.
2) They contact each other.
3) They are all attached to the basement membrane.
4) They are polar (have an “up” side and a “down” side).

Question 10

In the beginning, in which direction do carcenogenic epithelial cells proliferate?

Answer 10

Into the luminal space (or into the lumen)

Question 11

What event in epithelial cancer leads to metastasis?

Answer 11

When epithelial cells acquire mutations allowing them to chew through the basement membrane.

Question 12

What does a stalk of a colon polyp suggest?

Answer 12

That the cancer cells are already growing into the basement membrane.

Question 13

True or false: We now have a drug to treat a p53 mutation.

Answer 13

False

Question 14

Cancer that is benign; still comprised of cells that proliferate rapidly, but these cells are contained by the basement membrane (non-invasive).

Answer 14

Adenoma

Question 15

Cancer that is malignant; the cells have grown into or through the basement membrane.

Answer 15

Adenocarcinoma

Question 16

Benign cancer

Answer 16

Adenoma

Question 17

Malignant cancer

Answer 17

Adenocarcinoma

Question 18

What protein do epithelial cells contain that keeps them locked together? What happens to this protein during invasion or mestasis?

Answer 18

E-Cadherin; It is lost.

Question 19

What protein binds epithelial cells to the basement membrane? What happens to this protein during metastasis?

Answer 19

Integrins; It is lost.

Question 20

What two types of epithelial cell proteins are lost during metastasis (invasion of the basement membrane)?

Answer 20

1) E-cadherins - bind epithelial cells together

2) Integrins - bind epithelial cells to the basement membrane

Question 21

What is the process of getting rid of E-cadherins and integrins called?

Answer 21

EMT (epithelial to mesothymal transition)