2-14 thru 2-19 Flashcards
What is the genetics name for the short arm of the chromosome? The long arm?
p arm, the long arm is called the q arm
What is the difference between an oncogene and a tumor suppressor gene?
oncogenes= growth promoters, tumor suppressors = growth suppressors
What are the three functions of proto-oncogenes (when mutated, they become oncogenes)
promote cell division, differentiation, and stop cell death
What class of proteins are usually made from proto-oncogenes?
kinases
Why did scientists first believe that oncogenes were contagious
Src in rooster was the first identified oncogene, and it was known to originate from viral-induced mutation
By what 3 WAYS are proto-oncogenes activated
- one mutation needed to make hyper-activated as a gain-of-function mutation 2. gene is duplicated/ amplified and expression mevel is increased 3. gene is translocated to fuse with another gene, making it basally active
What kind of molecules are growth factor receptors?
receptor tyrosine kinases- dimerize to transphosphorylate
In what 3 WAYS are receptor tyrosine kinases made constitutively activated?
- affinity for transphosphorylating region increased 2. loss of extracellular control domain 3. overactive autocrine signalling
What are 2 commonly mutated growth factor proto-oncogenes
EGFR & HER2 (A.K.A. ERBB1 & 2)
What kind of mutation if HER2 known for?
gene amplification
What are the 3 proteins immediately downstream of ERBB receptors?
Ras, P13K, Raf
How does Ras function normally vs. when mutated to an oncogene
Ras is a GTPase that turns off when in GDP-bound form. When transformed into an oncogene, it does not care if GTP or GDP is bound- it is always active
What is the product of PIK3CA and what role does it play in cancer?
product= the catalytic residue of phosphotidylinositide-3-kinase (PI3K), a protein regulated by Ras or directly by growth factor receptors. When made constitutively active, it phosphorylates the 3’ Carbon of PIP3, signalling for cell growth
How does Adk relate to the ERBB pathway?
ERBB stimulates Ras, stimulates PI3K, stimulates PIP3, stimulates PH -> binds PDK1/Adk, PDK1 activates Adk
What is the difference between oncogene mutations and tumor suppressor mutations?
Oncogenes get gain-of-function mutations, tumor suppressors get loss-of-function mutations. Oncogenes get DOMINANT mutations, and tumor suppressors are recessive
What theory of tumor suppressor development was derived from the first tumor suppressor gene, Rb1
The two-hit hypothesis (one bad copy gives rise to cells that may develop “2nd hit” in the same cell or its progeny)
What is LOH? What does it refer to?
Loss-of-heterozygosity: referring to the 2-hit mechanism of tumor-suppresor derived cancer mutations
What are the 4 FUNCTIOS of tumor suppressors
- cell cycle check points 2. inhibition or regulation of cell cycle 3. promote apoptosis 4. participate in DNA repair
What is the R-point
restriction point in G1. when the cell receives signal from environment that its ok to replicate and makes a nearly ABSOLUTE commitment to replicate
What is the function of Rb
Rb gets phosphorylated by cyclin D/Cdk 4/6 complex. This inactivates Rb so it can’t block the TF that allows progression through cell cycle
How does normal functioning p16 prevent the cell from progressing through the cell cycle
prevents cyclin D from interacting with Cdk4/6
Name the ways the cell can bypass the R-point in cancer
By upregulating Cyclin D1 or Cdk 4/6 or Cyclin E or Cdk2 or making Rb more prone to hyperphosphorylation or blocking it from blocking the TF for commitment to cell cycle
what is the most frequently mutated gene of all cancers?
p 53 - it does EVERYTHING, determines if halted cell cycle should be repaired or trigger apoptosis
Why does The structures of p53 make it possible to give a dominant negative mutation if one allele is ‘hit’
It is a homotetramer TF
How is conc. of p53 regulated?
It is auto regulated by MCM2, stress blocks degradation of p53
What kind of mutation in p53 causes cancer
Decrease the activity of p53 so concentration of MCM2 is Kept low and concentration of p53 increases
What is PTEN’s normal function in the cell
Prevents PIP3 from being over-activated (phosphorylated), thus suspressing growth and survival signals of the PI3K pathway
Why is PTEN a weird enzyme
It is a lipid phosphotase rather than a protein phosphotase
How is PTEN deregulated in cancer
It is made less active or expressed at lower levels
What class of proteins are BRCA1, 2? are they related?
nuclear proteins that act in DNA repair (HDR). Not related
What is the effect of dysregulating BRCA1, 2? Is it usually a dominant or recessive mutation?
Dysregulating BRCA1 or 2 causes genome instability, ANEUPLOIDY, increasing the likelihood of mutation. It is a recessive mutation.
What 3 genes are mutated to cause loss of ability to senesce?
Rb1, p53, telomerase
Why do chr arms shorten?
RNA polymerase needs space to make the primer for replication
Is APC a tumor suppressor or an oncogene
tumor suppressor (LOH mutation needed)
What are the energetic differences of a resting cell versus and actively proliferating cell?
Metabolism is increased, as seen in an increase in cellular concentrations of glucose, glutamine, and lipids. Increased glycolytic rate means that cells are in a more acidic environment when cancerous
How is increased glycolysis detected in cancer?
Use of F-18-deoxyglucose and visualizing rate of uptake by PET scan
Warburg Effect
Increased uptake of glucose in cancer cells
Why do cancer cells display a high level of aerobic glycolysis?
They adapt from a hypoxic environment before angiogenesis phase
What metabolic adaptation allows tumor cells to become invasive
ability to thrive in acidic environment
Which class of cancer genes directly increases the ability of the cell to upregulate intake of metabolites
oncogenes (like EGFR, PI3K, PTEN, etc.)
hTERT definition, and what class of cancer gene
telomerase. oncogene.
