Lecture 5 Flashcards
What is Ras? why is it seen in many cancers
Small GTPases that act as molecular switches by coupling cell membrane growth factor receptors to intracellular signalling pathways that regulate various cellular processes, monomeric, bind and hydrolyze guanine nucleotides. Seen in so many cancers because it is essential in signal transduction
how do Ras, HER2 and C-myc induce cancer
Ras: mutation
HER2-amplification
C-myc: translocation
what is EGFR
tyrosine kinase.
What is a tyrosine kinase
an enzyme that can transfer a phosphate group from ATP to a protein in a cell. On/off switch in many cellular functions
T/F phosphorylation is reversible
True
how does a proto-oncogene become and oncogene
Mutation
amplification
Gene translocation
What is EGF?
Hormones bind to EGF which cause dimerization of EGF monomers, which begins the activation cascade of the Ras protein
Describe Ras protein activation
Hormones bind to EGF monomers which cause dimerization, and phosphorylation of receptor tyrosine residues
GRB2 and Sos couples receptor to inactive Ras
GDP dissociates from Ras, GTP binds and active Ras dissociates from Sos
What’s the function of Sos in the third step of Ras activation
Promotes dissociation of GDP
What do GAP and GEF do?
GAP: Inactivates Ras
GEF: activates Ras
which codon mutations are the most common in cancer?
12
What mutation is responsible for H-ras oncogene activation?
V12, single base-pair mutation, glycine to valine, impairs GTPase activity
What is Ras binding to when it is active? inactive?
Active: GTP
inactive: GDP
why does the Ras protein activation/inactivation cycle run in one direction?
Hydrolysis of GTP to GDP is irreversible
which cancer is the most common to see a point-mutate ras gene
pancreatic cancer, 90% of pancreatic cancers have point mutated ras gene
What’s EGFR?
tyrosine kinase
What is a tyrosine kinase
transfers phosphate group from ATP to a protein in a cell. On/off switch in many functions.
What does EGFR do in a normal cell?
increases gene transcription and cell cycle progression
What cancer is HER2 linked to
breast & ovarian cancers
What is Burkitt’s Lymphoma
Malignant neoplasm in bone marrow and lymphatic structures
Cancer in the lymphatic system (B-lymphocytes), extreme proliferation
extremely high proliferation rate
occurs a lot in equatorial Africa
distinct jawbone
three types
What are the three types of BL
Endemic, Sporadic, Immunodeficiency-associated
What is Sporadic BL?
affects the whole world, mainly in kids, not linked to EBV, abdomen affected
How is c-MYC translocated in BL
Translocated from chromosome 8 to IgH on chromosome 14 resulting in abnormal c-MYC expression and cell transformation
What is c-Myc? what is it’s function
Proto-Oncogene, causes cancer when the gene for c-Myc is translocated, located on chromosome 8, regulates B-cell survival and expression, and controls a variety of cell functions like cell cycle progression
how is c-MYC affected when its gene is translocated
The IgH enhancer directs high constitutive expression of IgH gene, when the c-MYC is translocated to this chromosome, it starts to produce c-MYC at exceptionally high amounts
how are B cells and immunoglobulins related?
B cells express IgH on their membranes
where are B cells mostly localized
cortex of lymph nodes
what are lymph nodes
filters foreign via lymphatic vessels, foreign antigens are trapped and exposed to immune system for destruction
What is CML? How is it caused
Chronic myelogenous leukemia, cancer of the white blood cells
Translocation between chromosome 22 and 9 resulting in BCR-ABL gene
describe Abl
On chromosome 9, non-receptor tyrosine kinase, regualtes cell proliferation, cell migration, actin reorganization, etc
Describe BCR
On chromosome 22, not a b cell receptor, serine/threonine kinase activity, cell cycle regulation
