PATH: Cell Cycle and Mechanisms of Cancer Development

Question 1

Non-cancerous cells must acquire mutations that allow what 5 key capabilities to develop into cancer?

Answer 1

Unregulated cell growth, avoid apoptosis and cell death, replicate and divide indefinitely, promote its own angiogenesis, and become capable of tissue invasion and metastasis

Question 2

By what general mechanisms can cells acquire unregulated cell growth?

Answer 2

Unregulated or altered cell cycle progression; acquisition of independence from external growth signals; and insensitivity to external anti-growth signals

Question 3

What is an oncogene?

Answer 3

A gene whose normal activity promotes cellular proliferation or division

Question 4

What is a tumor suppressor gene?

Answer 4

A gene that inhibits events leading towards cancer

Question 5

Do oncogenes and tumor suppressor genes work through a dominant or recessive manner?

Answer 5

Oncogenes through dominant and TS through recessive

Question 6

What is the most heavily regulated part of the cell cycle?

Answer 6

G1 phase

Question 7

Describe the regulation of E2F and Rb

Answer 7

E2F is a transcription factor that promotes cellular proliferation, and, under resting conditions is sequestered by Rb. Phosphorylation of Rb by cyclin-CDK complexes induces release of E2F by Rb. CDK can be inhibited by CDK inhibitors

Question 8

What are the three main checkpoints in the cell cycle that are critical for cancer development?

Answer 8

G1-S checkpoint; G2-M checkpoint; and spindle checkpoint

Question 9

What must happen for Retinoblastoma to occur?

Answer 9

It develops if 2 mutations inactivate both copies of Rb in the same cell

Question 10

What proteins mediate the compaction of DNA into chromosomes?

Answer 10

Cohesins and condesins

Question 11

What events occur in prophase of mitosis?

Answer 11

Compaction of DNA and breakdown of nuclear envelope

Question 12

What events occur in metaphase of mitosis?

Answer 12

ALignment of sister chromatids in the center of the cell, formation of mitotic spindles and kinetochores, attachment of microtubules to kinetochores

Question 13

What events occur in anaphase of mitosis?

Answer 13

Proteolytic degradation of cohesin, triggering chromosome segregation and movement of sister chromatids toward poles

Question 14

What events occur in telophase of mitosis?

Answer 14

Reformation of the nuclear envelope

Question 15

What is aneuploidy?

Answer 15

The state of having an incorrect number of chromosomes

Question 16

What is Large scale genomic instability?

Answer 16

The presence of alterations in the number or structure of chromosomes (aneuploidy, chromosomal rearrangements, chromosomal breakages, etc. )

Question 17

What are the four basic ways a proto-oncogene can be activated to an oncogene?

Answer 17

1) Acquisition of a point mutation resulting in a constitutively active protein 2) Amplification (increase # of gene copies) 3) Upregulation of protein 4) Translocation resulting in fusion protein

Question 18

What is the mechanism by which Ras becomes an oncogene?

Answer 18

Pt mutation resulting in an inability of Ras to hydrolyze GTP, resulting in a constituitively active MAP K pathway

Question 19

What kind of protein is HER2? What makes it an oncogene?

Answer 19

Tyrosine Kinase Receptor; Amplification or Upregulation

Question 20

How is the Philidelphia chromosome made? What abnormal protein is made and what does it cause?

Answer 20

Chromosomal translocation t(9;22)(p34;p11) creating Bcr-abl which causes Chronic Myelogenous Leukemia

Question 21

How does p53 play a role in regulating cellular life?

Answer 21

When there is significant DNA damage, p53, a transcription factor, is expressed and upregulates the expression of pro-apoptotic Bax, Bak, and Bad proteins

Question 22

What are the major anti-apoptotic proteins that inhibit Bax and Bak? By what are they inhibited?

Answer 22

Bcl-2 and Bcl-XL; Bad

Question 23

What is the function of MDM2?

Answer 23

Promotes the degradation of p53

Question 24

Almost 50% of cancers have a mutation in what gene?

Answer 24

p53