Molecular Oncogenesis Flashcards
What are typical genes that are altered that can cause cancer?
- Proto-oncogenes
- Tumor Suppressor
- Anti-apoptosis
- Apoptosis genes
- DNA repair
How can growth factors and their receptors contribute to cancer?
Some cells gain the ability to produce growth factors that will continually allow them to proliferate
Typically growth factor receptors are expressed intermittently, but an alteration may overexpress allowing frequent activation - Tyrosine Kinase activation of many pathways.
What is commonly over expressed in astrocytoma and osteosarcoma?
SIS gene is altered and overexpresses Beta-PDGF
What gene product is amplified commonly in breast cancer and what drug therapy can be used against it?
ERB-B2 produces overexpression HER2 tyrosine-kinase growth factor receptors.
Trastuzumab antibody that blocks the receptor from binding the growth factor
If a patient was identified to have a c-KIT gene mutation producing GISTs what might be a viable therapuetic?
Imatinib - blocks tyrosine kinase activity
If a patient has analysis performed his cancer and it identifies a RAS mutation, what does that mean?
Secondary messenger mutation that can continue giving a growth signal, even when there is no stimulus.
–Usually a GTPase (breaks down GTP when in active form), so may be unable to deactive the GTP-activated protein.
How does a c-ABL gene contribute to cancer?
The abl-gene is translocated from the #9 chromosome to #22 where it combines with bcr-gene and loses regulation of the tyrosine kinase receptor.
What drug therapy can be used on a c-ABL gene translocation?
Imatinib - blocks the tyrosine kinase activity
What is a major transcription factor associated with cancers that is mutated?
MYC-oncogene, activates many genes and when altered causes constant stimulation.
What is a common abnormality of the c-MYC gene?
Translocation from #8 to #14 and it’s placed next to the Ig-gene, which is stimulated frequently also activating the c-MYC gene causing frequent activation.
–Burkitt Lymphoma, B-cell tumors
How is the n-MYC different from the c-MYC and what does it indicate?
n-MYC can amplify itself constantly signaling activation, frequently involved in neuroblastoma. If n-MYC is found indicates poor prognosis. Tested for via FISH analysis.
What is Cyclin D’s relationship with Rb protein?
As the cell is growing in G1 phase a build up of CyclinD activates CDK4, which phosphorylates Rb allowing the cell to transition into S-phase.
How can Cyclin D1 be involved in cancer?
Translocation of #11 to #14 fusing IgH-D1, causing an over expression and increased cell cycle progression.
What is the two hit hypothesis?
Tumor suppressor genes have a pair of genes and must be altered to promote cancer growth.
How does the Rb gene regulate the cell cycle?
Rb binds E2F until Cyclin D activates CDK4, that phosphorylates Rb releasing E2F that allows progression of the cell cycle. If Rb dysfunctional then E2F can continually activate cell cycle progression
