Cancer Hallmarks Flashcards
What is cancer
Uncontrolled proliferation of any cell due to faulty or missing signals that result in benign or malignant tumors
What is the 2 categories of cancer causes
- Hereditary
- Environmental
What is hereditary factors influence on cancer development
<10% cancer cases
Wide range of genetic factors that can be influenced after exposure to potential carcinogens
What is the 3 environmental factors causing cancer
- Chemical
- Radiation
- Infectious agents
How does chemical exposure cause cancer
Most common
Damage DNA directly or indirectly & causes cancer if key genes are affected
How does radiation exposure cause cancer
Damage DNA if exposed to UV, x-ray or gamma radiation
How does infectious agents cause cancer
Virus integrate into host DNA & effect gene expression
Bacteria cause chronic inflammation
What occurs in the G1 & S phase
G1: cell growth
S: DNA replication
What is the functions of control points
Ensure DNA integrity & if DNA errors the cycle will stop/repair/apoptosis
What control G1/S transition
P53
What proteins control transition between phases
Mitosis promoting factors, MPF
What is MPF’s composition
Protein dimer made of cyclin & cyclin dependent kinase (Cdk)
How does MPF become activated
Cyclin binds to Cdk & activated Cdk to phosphorylated other proteins causing activation & degradation of other proteins & cell transition between phases
What is the protein dimer is present mid G1
Retinoblastoma protein & transcriptional factor E2F
How does activation of pRB happen
After activation of Cdk it targets pRB that is phosphorylated & cause confirmation changes & E2F is released, activated & can bind to upstream genes that initiate expression of other cycling & genes form DNA replication
What is cyclin E effect on increasing own transcription
Phosphorylate more pRB to further activate E2F & promote more cyclone E expression or increase own expressions
What is cyclin E function
Progress cell cycle from G1 to S phase when interacting with Cdk2
What is somatic mutation theory
Over time exposure accumulation of multiple mutations in different genes but same cell that forms cancer cells
What is the 3 types of cancer therapy
Surgery
Radiation therapy
Chemotherapy
What is HPV effect on the cell cycle
Express E6 & E7 that inactivate regulatory gene products p53 & pRB
What is E7 effects on cell cycle
E7 binds to pRB & can’t bind E2F & released from pRB & bind promotor of target genes & transcribed gene products drive cell into S phase
What is E6 effects on cell cycle
E6 produce a protein that binds & inactive p53 that promotes unregulated cell division, cell growth, cell survival all characteristics of cancer
What is the normal function of p53
Prevent cell growth & promote cell death when there is DNA damage
Upregulate p21 protein which block formation of cyclin D & Cdk4 complex that prevent pRB phosphorylation that halts the cell cycle progression by preventing activation of E2F
What is HPV net effect on cell
Increased proliferation & avoidance of apoptosis despite DNA damage that can result in cervical cancer
What is the relationship between epigenetic and cancer
Cancer cells have a change in methylation pattern of DNA that changes expression profile of affected gene & methylation is at the promotor region that block gene transcription
Loss of methylation activates gene & allow transcription when transcription factor binds
What is the model of tumourigenesis
Carcinogens is a multi-step & multi gene model
Multistep: accumulations happen over time & not all at once
Multi gene: multiple genes are altered by mutation in the same cell
Long term exposure = development of cancer
What happens if alteration in genes happen in regulatory circuit
Dysregulation of critical homeostatic pathways
Can different cancers arise form different alterations of gene
Yes
What proteins does chemotherapy target & why
Chemotherapy targets Ras protein
Central role in cellular process look proliferation, cell cycle progression, apoptosis & cell motility
