Carcinogenesis part II Flashcards
What are key categories of oncogenes?
growth factors, growth factor receptors, signal transducers, nuclear regulators, and cell cycle regulators.
remember:
cell has a GF receptor. when it needs to divide, GF binds the GF receptor. sends a signal carried by the signal transducer to the nucleus. within the nucleus, nuclear factors cause cell to cycle (involves cell cycle regulators). mutations in any of these steps can result in protooncogene
What should I know about PDGFB?
astrocytes in the brain has a PDGF receptor. if astrocytes overproduce PDGF, it will hit its own receptor. this overexpression causes an autocrine loop that causes an astrocytoma
What are some important growth factor receptors that can be mutated?
HER2/neu, RET, KIT
How does HER2/neu casue cancer? How do you treat?
this is an epidermal growth factor receptor that becomes amplified in a subset of breast cancer
treat with trastusumab/herceptin
What is the function, mechanism, and association of RET? Clinical significance?
neural GF receptor
point mutation
seen with MEN2A, MEN2B, and sporatic medullary carcinoma of the thyroid (common tumor btw MEN2A and 2B is medullary carcinoma). If pt has a RET mutation, you will prophylactically remove the thyroid.
What is the association of KIT?
gastrointestinal stromal tumor
What are important signal transducers that can be mutated?
RAS gene family, and ABL
What is the background biochemical mechanism of RAS?
when GF binds a receptor, RAS may be associated with the receptor. If ras is associated with the receptor, it normally sits bound to GDP. When GF binds the receptor, the GDP gets kicked off of RAS. instead, RAS gets associated with GTP. RAS-GTP complex can send a signal to the nucleus to promote growth.
RAS also has the ability to cut away one of the phosphates, turning GTP to GDP and shutting off its own function. GAP is also associated with RAS to help it inactivate itself. Many RAS mutations involve GAP. If GAP can’t associate with RAS, RAS will have a hard time shutting off function. If RAS remains associated with GTP, we see excess signal
What is the function, mechanism, and association of RAS?
association: carcinomas, melanoma, and lymphoma
mechanism: Point mutation, esp. with GAP
this is a GTP binding protein
What is the function, mechanism, and association of ABL?
tyrosine kinase
often a t(9,22) translocation. associated with CML and some types of ALL (esp. adult ALL- poor prognosis)
9;22 translocation defines CML
What are nuclear regulators can be mutated?
myc: c-myc, n-myc, and l-myc
What is the function, mechanism, and association of c-myc?
transcription factor.
seen in burkitt lymphoma
usually a translocation btw chromosome 8 and chromosome 14. remember that burkitt’s lymphoma is a lymphoma of B cells. Ig heavy chain sits on chromosome 14. this gene is basically always on. if there is a translocation of myc to chromosome 14, myc will always be turned on because the b cell always wants to make heavy chains.
“starry sky appearance”
What is the function, mechanism, and association of N-myc?
transcription factor
see amplification
causes neuroblastoma
What is the function, mechanism, and association of L-myc?
transcription factor, see amplification, causes lunc carcinoma (small cell)
What are important cell cycle regulators that can be mutated in cancer? What step is most highly regulated
CCND1 (cyclin D) and CDK4:
these are proteins that assist movement through the cell cycle. G1 to S phase (synthesis phase) is the most highly regulated.
