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LIFE 210 (38)

Cancer, tumor suppressor genes, P53, treatment, prevention

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Life Science
LIFE 210
Paul Laybourn

9 December Cancer is caused by loss or gain of functions Tumor suppressor genes: loss of an inhibitory function; recessive mechanism and requires loss of both copies Oncogenes: gain of function of a stimulatory protein; act in a dominant fashion and require only one copy to be mutated Mutations can occur through large, global chromosomal changes or small changes to nucleotides in DNA Multiple mutations are needed for a cell to become cancerous Cancer cells reproduce in defiance of normal restraints of cell growth/division Mutations accumulate over time and as a result of previous mutations Mutations that cause cells to ignore signals are common in cancer Mutated proteins are generally in a signaling or repair pathways Myc, Ras, APC, Rb, and p53 mutations are common in cancers Mutations that deregulate cell division P16 is produced in response to cell stress to stop growth/division Rb is a tumor suppressor and functions as a pocket protein Rb inhibits E2F (a promoter for transcription factors required for entry into S phase) Extracellular signals for growth and division A mitogen triggers cell division (mitosis) A growth factor can stimulate growth, proliferation (division), and differentiation Mitogens, growth factors, and downstream signaling targets are often proto-oncogenes P53 is an oncogene that is mutated in many cancers Activate DNA repair proteins upon DNA damage Induce growth arrest on DNA damage recognition Initiate apoptosis p53 mutation allows for more downstream mutations and allows for genetic instability Genetic instability leads to additional mutations Removing/inactivating p53 allows cells to divide with DNA damage Larger scale chromosome changes occur as a result Accumulation of mutations correlates with aggressive, malignant tumors Viruses can also cause cancer Viruses hijack host proteins to reproduce viral genome (DNA viruses) Viral genomes are integrated into host genome Human papillomavirus (HPV) Human papillomavirus acts through Rb and p53 to cause cancer HPV early genes E6 and E7 act as oncogenes Responsible for 5.2% of new cases of cancer Higher risk for women (cervical cancer, cell type specific effect) Metastasis is a bad sign Unknown what makes some cancers metastatic Tumor migration: local invasion and metastasis Circulating cancers (leukemia) are more likely to be metastatic Once colonization occurs, it makes treatment much more difficult
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