Cancer II

Question 1

What are the two major categories of tumor suppressor genes?

Answer 1

Proteins that normally restrict cell growth and proliferation
Proteins that maintain integrity of the genome

Question 2

What are some tumor suppressor proteins that normally restrict cell growth and proliferation

Answer 2

Intracellular proteins that inhibit progression through G1 in the cell cycle (Rb, CKI)
Receptors or components of a signaling pathway that inhibit cell proliferation
Proteins that promote apoptosis

Question 3

What are some tumor suppressor proteins that maintain integrity of the genome?

Answer 3

Checkpoint control proteins (ATM, ATR-detect DNA damage - stops cell cycle) - Ataxia Telangiectasia
DNA repair enzymes or pathways

Question 4

What is retinoblastoma?

Answer 4

Inherited eye cancer in children. rare and occurs before age 2
Diagnosed before age 5
Involves Rb - a tumor suppressor that inhibits cell division

Question 5

What are the two forms of retinoblastoma?

Answer 5

Hereditary (40%-both eyes) and sporadic form(60%-one eye)

Question 6

Describe hereditary form Rb

Answer 6

Loss of function or deletion of one copy of Rb in every cell

Somatic event occurs and eliminates one good copy and tumor forms. thus a loss of heterozygosity

Question 7

Describe sporadic form Rb

Answer 7

non-hereditary
two hit hypothesis- first Rb gene obtains mutation then needs second mutation Rb
More rare than hereditary form

Question 8

What are proto-oncogenes?

Answer 8

Normal gene, usually involved in regulation of cell proliferation that can be converted to a cancer-causing oncogene by a mutation (overactivity mutations)

Question 9

What are the four functions of cancer genes?

Answer 9

Regulate cell proliferation
Control cell growth
Control division
Control apoptosis

Question 10

Cdk or cyclin:

A proto-oncogene or a tumor suppressor gene?

Answer 10

Proto-oncogene

Active CKI stops Cdk
Rb binds E2F

Question 11

CKI or Rb:

A proto-oncogene or a tumor suppressor gene?

Answer 11

Tumor suppressor gene

CKI absent so Cdk always active
Rb inactive and E2F drives S-Cdk activation by making more cyclins

Question 12

What is the guardian of the genome?

Answer 12

p53: huge tumor suppressor gene
Involved in:
Cell cycle arrest
DNA repair
Apoptosis
Block of angiogenesis

Question 13

If you lose p53, what functions will be lost?

Answer 13

1. loss of checkpoint control in cell cycle
2. loss of cell cycle arrest in response to DNA damage
3. loss of apoptosis in response to DNA damage
4. loss of DNA repair activities

Question 14

How is p53 associated with p21 and pro-apoptotic proteins?

Answer 14

p53 upregulates p21

p53 activates expression of pro-apoptotic proteins

Question 15

Bcl2:

proto-oncogene or tumor suppressor?

Answer 15

proto-oncogene

Question 16

What is papilloma virus?

Answer 16

Warts and cervical cancer
If tumor integrates with host DNA it interferes with control of cell division in basal cells and a malignant tumor develops
E6 and E7 cause malignancy and they bind to p53 and Rb, respectively
The cells then can replicate in an uncontrolled manner
too much cyclins and no CKI available

Question 17

For most cancers what is the first step of metastasis?

Answer 17

Local invasion and only a few cancer cells will pass this barrier
-difficult

Question 18

What is the initial entry into blood or lympathic vessels facilitated by?

Answer 18

Angiogenesis of new blood or lympathic vessels

-most cancer cells have acquire this ability before becoming invasive through mutations in genes that control apoptosis

Question 19

How are cancer cells colonized at remote sites?

Answer 19

They survive in circulation and exit at remote sites
Some cells die after they enter a foreign tissues, others fail to proliferate, or only form micro-metastasis
Only a few continue to proliferate and colonize

Question 20

What is one of the most preventable cancers and why?

Answer 20

Colorectal cancer
Colonoscopy reveals early detection
Takes 10 years for tumor progression so there is lots of time to check

Question 21

Where does colorectal cancer arise?

Answer 21

in the epithelial lining of large intestine

Mutations that disrupt organization signals begin tumor progression for colorectal cancer

Question 22

What is a small,protruding benign tumor called?

Answer 22

polyp: adenoma
Precursor of colorectal cancer
Cut it off and itss a cure

Question 23

What are the common mutations in colorectal cancer?

Answer 23

40% have point mutation in K-Ras
60% inactivating mutation of p53
Important loss is APC mutation

Question 24

what is familial adenomatous polyposis coli?

Answer 24

hereditary colorectal cancer
Hundreds of polyps 
At least one will become malignant
Caused by inactivation of tumor suppressor gene APC
LOH

Question 25

What is HPNCC?

Answer 25

hereditary non-polyposis colorectal cancer
Unusual
Most have normal # or near-normal # of chromosomes
Colorectal cancer cells usually have multiple copies of chromosomes

Question 26

What is chemotherapy

Answer 26

Drugs that treat cancer
Stops cell division - impact on rapidly dividing cells like cancer cells but also stops follicle cells produce hair, stomach-lining cells, blood-producing cells

Question 27

What is responsible for chronic myelogenous leukemia?

Answer 27

Reciprocal translocation between chromosomes 9 and 22

• philadelphia chromosome
• Bcr-Abl

Question 28

Describe Bcr-Abl

Answer 28

Abl - tyrosine kinase for cell signaling
N-terminus Bcr makes it hyperactive
Coding sequence of Bcr is fused to Abl when chromosomal translocation occurs
Bcr-Able makes highly active tyrosine kinases and is highly expressed
->CML

Question 29

What is the treatment for CML?

Answer 29

Gleevec: inhibits tyrosine kinase activity
Causes disappearance of Philadelphia crh in most patients
Gleevec takes place of ATP on Bcr-Abl-substrate not changed: competitive inhibitor

Question 30

What is combination therapy?

Answer 30

treat patients with drugs simultaneously is an advantage for cancery therapy
fight those rare mutant cells that are resistant to one drug and then go on to proliferate to form new tumor

Question 31

How can microarray be used to fight cancer?

Answer 31

Gene expression profile of a cancer can be analyzed by microarray to identify disregulated cancer-critical genes
Custom-driven treatments can be selected to target specific disregulated cancer-critical proteins
Presonalized medicine

Question 32

What therapy has Folkman created?

Answer 32

Anti-angiogenesis therapy

The idea that cancerous tumors require formation of new blood vessels- if prevented, starve tumors

Question 33

What are tumor suppressor genes?

Answer 33

Genes that generally encode proteins that inhibit cell proliferation