PATH: Cell Cycle and Mechanisms of Cancer Development Flashcards
Non-cancerous cells must acquire mutations that allow what 5 key capabilities to develop into cancer?
Unregulated cell growth, avoid apoptosis and cell death, replicate and divide indefinitely, promote its own angiogenesis, and become capable of tissue invasion and metastasis
By what general mechanisms can cells acquire unregulated cell growth?
Unregulated or altered cell cycle progression; acquisition of independence from external growth signals; and insensitivity to external anti-growth signals
What is an oncogene?
A gene whose normal activity promotes cellular proliferation or division
What is a tumor suppressor gene?
A gene that inhibits events leading towards cancer
Do oncogenes and tumor suppressor genes work through a dominant or recessive manner?
Oncogenes through dominant and TS through recessive
What is the most heavily regulated part of the cell cycle?
G1 phase
Describe the regulation of E2F and Rb
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
What are the three main checkpoints in the cell cycle that are critical for cancer development?
G1-S checkpoint; G2-M checkpoint; and spindle checkpoint
What must happen for Retinoblastoma to occur?
It develops if 2 mutations inactivate both copies of Rb in the same cell
What proteins mediate the compaction of DNA into chromosomes?
Cohesins and condesins
What events occur in prophase of mitosis?
Compaction of DNA and breakdown of nuclear envelope
What events occur in metaphase of mitosis?
ALignment of sister chromatids in the center of the cell, formation of mitotic spindles and kinetochores, attachment of microtubules to kinetochores
What events occur in anaphase of mitosis?
Proteolytic degradation of cohesin, triggering chromosome segregation and movement of sister chromatids toward poles
What events occur in telophase of mitosis?
Reformation of the nuclear envelope
What is aneuploidy?
The state of having an incorrect number of chromosomes
What is Large scale genomic instability?
The presence of alterations in the number or structure of chromosomes (aneuploidy, chromosomal rearrangements, chromosomal breakages, etc. )
What are the four basic ways a proto-oncogene can be activated to an oncogene?
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
What is the mechanism by which Ras becomes an oncogene?
Pt mutation resulting in an inability of Ras to hydrolyze GTP, resulting in a constituitively active MAP K pathway
What kind of protein is HER2? What makes it an oncogene?
Tyrosine Kinase Receptor; Amplification or Upregulation
How is the Philidelphia chromosome made? What abnormal protein is made and what does it cause?
Chromosomal translocation t(9;22)(p34;p11) creating Bcr-abl which causes Chronic Myelogenous Leukemia
How does p53 play a role in regulating cellular life?
When there is significant DNA damage, p53, a transcription factor, is expressed and upregulates the expression of pro-apoptotic Bax, Bak, and Bad proteins
What are the major anti-apoptotic proteins that inhibit Bax and Bak? By what are they inhibited?
Bcl-2 and Bcl-XL; Bad
What is the function of MDM2?
Promotes the degradation of p53
Almost 50% of cancers have a mutation in what gene?
p53
