CA Flashcards
What are the three types of genes that CA cells change?
- proto onco genes
- Tumor suppressor genes
- caretaker genes
What is the mutational function of protoonco genes?
Converted to oncogenes that increase cell division
What is the mutational function of Tumor suppressor genes?
Will not turn off cell growth
What is the mutational function of Caretaker genes?
Do not prevent/repair DNA mutations
What are the 6 traits that a cell must obtain in order to become metastatic CA?
- self sufficiency in growth
- Insensitivity to antigrowth signals
- Evading apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Tissue invasion and metastasis
True or false: conversion of a proto-onco gene to an oncogene changes the activity of the protein itself
False- only results in excess production of the protein, or disrupts the normal control of the proteins function
The receptor for epidermal growth factor, which is a tyrosine kinase, is called what?
ErbB1 or HER2
What type of cascade does EGF act through?
MAP kinase cascade
How does ErbB1 become mutated?
remove the signal receptor
How does HER2 become mutated?
Dimerization in the absence of ligand due to changes in the plasma membrane spanning portion
How is Ras mutated?
point changes in amino acids leads to constant activation
How are c-Fos and c-Myc mutated?
Stabilization
Normally they are unstable. DNA changes = stabilization
What is Burkitt’s lymphoma?
Increased in Myc activity
translocation of Myc from chromosome 8 to chromosome 14= incrased transcription
In general, are oncogenes on dominant alleles or recessive allele?
Dominant
In general, are tumor suppressor genes on dominant alleles or recessive allele?
Recessive
What needs to happen in the “two hit” model of CA proliferation in tumor suppressor gene for CA to develop?
Need one somatic mutation to develop CA cells
(Since tumor suppression genes are typically recessive genes, individuals can be carriers for mutant suppressor genes. Thus only a single allele needs to be mutated)
What is retinoblastoma?
CA caused by a mutation of the Rb protein gene, causing no Rb to be produced.
(note that this is a recessive allele in herditary form. Somatic form do not inherit any mutated allele.
Also, recall how Rb inhibits E2F)
What is the protein that associates with p53, makes it likely to be ubiquinated, and therefore likely to be degraded by proteosome?
Mdm2
What happens when p53 is phosphorylated by ATM or ATR? What molecule does p53 increase?
Stabilized
p21^CIP1
What is the most common genetic alteration in human CAs?
Mutations in p53
p53 is a homotetramer. How does this fact contribute to how mutations in the gene for p53 lead to cancer?
Makes it a dominant type of mutation
a mutation will lead to incorrect protein in all tetramers since they are all the same
What is Li-Fraumeni syndrome? What causes it?
Disease characterized by a propensity to develop a wide variety of tumors.
A mutation in the p53 allele.
HPV produces two proteins called what? What two proteins do they suppress?
E6 and E7
Both repress Rb, and p53
What causes neurofibromatosis?
Recessive gene mutation in NF1 that result in changes in neurofibromin
(neurofibromin functions to accelerate Ras hydrolysis–mutation= prolonged Ras)
What is the protein involved in neurofibromatosis? Symptoms?
Neurofibromin
CA cells around neuronal sheaths
What is the cause of HBOC syndrome? Is this a recessive or dominant trait?
Mutation in BRCA1 and BRCA2 genes.
Dominant