Neoplasia (7) - Self-sufficiency in Growth Signaling Flashcards
Germline mutations
Heritable!
- DNA is mutated from the beginning of development
Germline mutations are seen in what type of cancer syndromes?
Familial
Somatic mutations
NON-heritable; Acquired over lifetime
With Proto-oncogenes, how does cancer arise?
A mutation = Gain of function
With Tumor-suppressor genes, how does cancer arise?
2 mutations = Loss of function
With Apoptosis regulating genes, how does cancer arise?
Suppress Apoptosis
With DNA repair genes, how does cancer arise?
Loss of function
Driver mutations
CAUSE cell growth
Passenger mutations
Do not directly cause cancer but are along for the ride with driver mutations
Normal gene that when mutated, becomes an oncogene
Proto-oncogene
Mutated gene that results in excessive cell growth
Oncogene
Amplification of Growth receptors on the cell membrane result in?
More receptors create more opportunities for growth factors to stimulate cell proliferation and growth!
What is an example of an amplification of a growth receptor that results in cancer?
Her-2/neu results in breast cancer
How do you treat breast cancer that was caused by Her-2/neu growth receptor amplification?
Herceptin - antibodies to the Her-2/neu receptors on the cell inhibit growth factors from binding and activating the cell to grow
What does RAS normally do?
Activates all downstream cell events for growth and proliferation after a growth hormone binds the growth receptor on the cell
When RAS is active, what is it bound to?
GTP
When RAS is inactive, what is it bound to?
GDP
Point mutations in RAS will cause?
RAS will be constitutively active and stuck to GTP; even in no presence of a growth factor!!
With what cancers are point mutations in RAS that cause it to be stuck to GTP and always active seen?
Pancreas, lung and colon cancers
Normal job of PTEN?
INHIBITS p13k pathway that RAS-GTP activates
– STOPS the cell signaling
When PTEN is inactive, what occurs?
RAS-GTP activates the P13K pathway and cell signaling/growth occurs!
A loss of function mutation of PTEN is seen with what cancer?
Endometrial carcinomas
Endometrial cancers have a loss of function mutation in PTEN. Describe what happens.
RAS-GTP is active and activates the P13K pathway. With NO PTEN to STOP this p13k pathway, cell growth and proliferation signals are passed on!
With Chronic Myeloid Leukemia, what chromosomal abnormality is present?
Translocation
With Chronic Myeloid Leukemia, what genes are translocated to be together?
BCR-ABL
What does the BCR-ABL translocation activate and what does that ultimately result in?
Activates Tyrosine Kinases that stimulate growth
= Chronic Myeloid Leukemia
What is oncogene addiction?
Tumor genesis is DEPENDENT on a particular protein
What is an example of oncogene addiction?
BCR-ABL with chronic myeloid leukemia
How can you treat chronic myeloid leukemia?
Tyrosine Kinase INHIBITORS
– Blocks the Tyrosine Kinases that BCR-ABL is activating for cell growth
What is MYC?
Master transcriptional regulator
If MYC is active, what is increased?
MYC is a transcription agent
= INCREASED Protein synthesis and thus cell growth
Amplification of MYC is seen with what cancer?
Neuroblastoma
Neuroblastoma often affects what population?
Children
Neuroblastoma has an amplification of?
MYC
If Cyclin D1 is active, what will result?
Cell cycle is ACTIVE
If Cyclin D1 is inactive, what will result?
NO CELL CYCLE OCCURRING
With what cancer is Cyclin D1 always active and stimulating the cell cycle to occur?
Mantle cell lymphoma
Normally, what is the job of P16?
INHIBITS Cyclin D1 and thus INHIBITS the cell cycle from occurring
P16 inhibits ____
Cyclin D1
- And thus the cell cycle
Germline loss of P16 creates what type of cancer?
FAMILIAL Melanomas - inherited
If P16 loses function, what results?
It canNOT inhibit Cyclin D1, so the cell cycle will progress and cell growth and proliferation will occur
