Cancer/ Oncogenesis Info Flashcards
What are cancer cells?
Transformed cells capable of uncontrolled proliferation
Cellular growth and proliferation are controlled by?
cytokines that upon binding to their respective receptors signal via cellular signaling pathways (MAP kinase pathway) to elicit growth and cell proliferation.
What could potentially cause uncontrolled cellular prolif?
genetic mutations in any of the signaling proteins (tyrosine kinase, monomeric G protein Ras, etc)
Genes that could potentially cause transformation are called?
proto-oncogenes
Mutated versions of proto-oncogenes that cause cancer are called?
Oncogenes (eg, src, ras, myc, abl, etc.)
An RNA tumor virus is…
a certain cancer causing retrovirus
Cancer causing retroviruses (RNA tumor virus) contain…
viral oncogenes derived from host cell genome and cause virus-induced cancers upon infection
The antigens of ________ cause tumors that have no cellular counterparts. Egs are:
DNA Tumor Viruses
eg; papiloma virus, adenovirus, polyomavirus
DNA tumor virus antigens bind and inhibit proteins encoded by
tumor suppresor genes
Tumor suppressor genes are responsible for…
cell cycle check points and prevent cells containing DNA lesions from completing the cell cycle
Cells with irreparable DNA damage are triggered into…
programmed cell death (apoptosis)
What protein triggers apoptosis?
p53 and others
Some genes are proapoptotic:
Bad, Bix
Genes that are anti-apoptotic:
Bcl2, Bcl-XL
For cancer to occur, what must happen?
multiple lesions in the DNA must occur resulting in the activation of oncogenes and inactivation of tumor suppressor genes
Overexpression of what genes could also cause cancer?
Bcl2- anti-apoptotic genes
Cancer chemo agents and non-chemo agents are aimed at:
1) Preventing cellular proliferation and causing cell death by disrupting DNA metabolism.
2) Cause direct DNA damage resulting in mutations, DNA strand scission, DNA cross linking or indirectly inhibition, disruption of DNA biosynthesis
What do the M phase disruptors do?
they interfere with tubulin polymerization/ deopolymerization and disrupt mitotic spindle fxn.
How does retinoic acid work?
Cuases cancer cells to terminally differentiate and thus lose their ability to prolif.
Cancer chemo agents are under two categories:
1) Cell-cycle specific agents (CCS)
2) Cell cycle non-specific agents (CCNS)
Resistance to cancer chemo drugs is due to:
single gene mutations, gene amplification or by expression of multi-drug resistance surface membrane P-glycoprotein encoded by MDR1.
What increases resistance to drugs by functioning as drug export pumps?
MDR1- MDR9
Many cancer cells show chromosomal aberrations such as:
translocation (CML, Burkitt’s lymphoma)
Cancer occurs in what three stages?
1) Initiation- DNA damaging agents cause initiation
2) Promotion- cellular events that promote deregulated growth and cell division
3) Progression- cellular proliferation cancer stem cells
Agents that cause cancer are:
1) Heritable cancer- Ataxia, HNPCC, Breast
2) Exposure to ionizing radiation causing DNA strand scission
3) Exposure to UV radiation causes thymine dimer formation
4) Chemical carcinogens- DNA mutagenizing chemicals such as alkylating agents (benzopyrenes in cigarette smoke)
5) Certain chronic viral infxns (HPV, EBV, HBV, HBC, HTLV, Herpes-8- Kaposi’s sarcoma)