Miles - Cancer Bio 2

Question 1

What are the three major occurrences of cancer initiation?

Answer 1

1. Activation of Proto-oncogenes 2. Inactivation of Tumor Suppressor Genes 3. Inactivation of Antimetastasis Genes

Question 2

What are the three major occurrences of cancer promotion?

Answer 2

1. Defects in terminal differentiation 2. Defects in growth control 3. Resistance to cytotoxicity

Question 3

Oncogenes

Answer 3

Genes that are “turned on” and have a stimulatory effect on cells.

• Proliferation
• Decreased requirement for growth factors
• Promotion of spreading
• Protection from apoptosis

Question 4

Tumor Suppressor Genes

Answer 4

Genes that are “turned off” in cancer.

Function is lost during tumor initiation/progression.

Question 5

Genomic Guardian Genes

Answer 5

Genes whose dysfunction may create genomic instability

e.g. DNA repair genes or recombination genes

p53

Question 6

Where were Oncogenes originally isolated from?

Answer 6

RNA Tumor Viruses ; originally thought to be part of the viral genome (v-onc); but now understood to be derived from host cell genome

Question 7

Proto-Oncogene

Is one change enough to create a tumor?

Answer 7

Normal cellular gene that is altered to a gene which can convert a normal cell to a tumor cell.

Conversion mechs:

Mutation

Translocation

Over-expression

Amplification

No, you need multiple for full cell transformation

Question 8

Ras

Answer 8

Oncogene affecting signal transduction

Question 9

Myc

Answer 9

Nuclear Oncogene

Transcription factor, Controlled by chromosomal translocation

Involved in cell-cycle regulation

Question 10

Burkitt’s Lymphomas

Answer 10

c-myc proto-oncogene translocated from chromosome 8 to chromosome 2

Results in abnormal c-myc expression

Question 11

Erb-2

Answer 11

Oncogene activation by gene amplification

Receptor protein-tyrosine kinase

Question 12

Tumor Suppressor Genes

Answer 12

Products negatively regulate cell growth or cell behavior

Function LOST during tumor initiation/profression

Occurs by LOH

Question 13

Loss of Heterozygosity (LOH)

Answer 13

Process by which tumor suppressor genes are lost.

Loss of an allele in tumor DNA compared to matched normal DNA from same individual

Question 14

Two Hit Hypothesis

Answer 14

First Hit = Inherited Mutation/Sporadic Mutation (heterozygosity protected)

Second Hit = Loss/Duplication/Recombination/Mutations/Methylation (Loss of Heterozygosity)

Question 15

Retinoblastoma

Answer 15

Tumor with genetic inheritance

Deletion in Rb gene; must lose both to cause disease (2-Hit Hypothesis)

Question 16

Inherited vs Non-inherited Retinoblastoma

Answer 16

Inherited = You have one defective copy, second hit gives you disease

Non-Inherited = Two random hits (rare)

Question 17

p53

Answer 17

Nuclear protein that increases in response to DNA damage

Increases expression of DNA repair enzymes; and/or apoptosis if damage is severe

Induces cell arrest (p21)

Many tumors knock p53 out

Question 18

How do malignant tumors invade tissue?

Answer 18

Through basement membrane into lymphatics/capillaries, must survive circulation, lead from capillaries and develope tumors in distant organs

Question 19

Angiogenesis Activators

Result if excessive?

Answer 19

VEGRs

Angiogenin

Renal disease, cancer, atheroscerosis, obesity

Question 20

Angiogenesis Inhibitors

Result if insufficient?

Answer 20

Angiostatin

Endostatin

Baldness, heartattack, limb fracturs, blood clots

Question 21

How did Folkman propose angiogenesis worked in tumors?

Answer 21

Tumor cells release angiogenic proteins, and supress angiogenic inhibtors

Question 22

Adenoma

Answer 22

Benign tumor arising from glandular epithelium

Question 23

What rate of cells will survive to form metastases?

Answer 23

< 1/1000