Unit III Week 1 Flashcards
Two major types of tumor initiation mutations
Activation mutation in oncogene
Inactivation mutation in tumor supressor gene
Importance of heredity in cancer
Cancer is not inherited (as single Mendelian) but accumulated over time with age.
Susceptibility to development can be inherited
Knudson’s Two Hit Hypothesis
Inherit one bad gene copy (hit 1)
Mutation/recombination/chr loss over life causes LOH (hit 2)
Familial retinoblastoma inheritance
Recessive disorder (dominant inheritance), but inheriting one bad copy generally results in cancer due to high LOH
Sporadic retinoblastoma inheritance
Recessive disorder, not strongly inherited
Functions of APC, BRCA1, BRCA2
Tumor suppressor genes
APC: prevents ß-catenin from entering nucleus
BRCA1/2: function in cell cycle checkpoints
Function of p53
Tumor suppressor gene
Transcription factor
DNA mutation repair in cell cycle (cell cycle arrest)
Apoptosis stimulating
Mutations of p53
Hotspot point mutations
Dominant negative mutations
RNA genome segments
gag: internal virion proteins
env: membrane glycoproteins
pol: virus polymerase
v-onc: necessary for malignancy
(v-src, v-erb, v-abl, v-myc)
Oncogene function: v-erb-B
Codes for protein similar to EGFR
Increases change of growth simulating properties
Tyrosine kinase activity
Oncogene function: v-abl
BCR-ABL
CML
Tyrosine kinase activty
Li-Fraumeni criteria
Autosomal dominant
~70% have p53 mutation
Hereditary and sporadic
Li-Fraumeni and Knudson’s Hypothesis
Hit 1: p53 point mutation Hit 2a: amplification of HER2 Hit 2b: EFGR mutation Hit 2c: changes to oncogene (Hit 2 can be on different gene)
Von Hippel-Lindau
Autosomal dominant
VHL gene = tumor suppressor
Penetrance >95% at 65 y/o (variability in severity)
Cystic and highly vascularized tumors in organs
Therapies to treat ccRCC
Majority are sporadic Local vs. metastatic Surgical resection/nephrectomy VEGF-R and MTOR inhibitors Immunotherapies
SREBP
SCAP
Cholesterol regulator
Binds bHLH transcription factor for LDLR and all 30 synthesis proteins (released by two step proteolysis RIP)
SCAP escorts SREBP to Golgi to trigger nuclear receptors
Under high cholesterol conditions, SCAP will be ________ with Insig
Bound to/associated with
Plasma volume
3 liters
ECF/ICF/3rd space volume
13/27/5
High concentration in ECF
Na+, Cl-
H2O equal
No A (large molecules)
High concentration in ICF
K+, A
H2O equal
Forces that determine gating properties
Temperature
Mechanical
Chemical
Electrical