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Mitogens stimulate G1-Cdk and G1/S-Cdk activities
p27 suppresses CdK activity
The Rb protein acts as a brake in mammalian cells
Excessive stimulation of mitogenic pathways
leads to cell cycle arrest or apoptosis
Cell growth like cell division is also stimulated
by extracellular signals
Comparison of nerve cell size vs. lymphocyte size
Cancer
Cancer incidence and mortality in the United States
Tumors can not be detected until 108 to 109 cells
are present
Why doesn’t cancer happen more often?
• 1016 cell divisions in a human lifetime.
• 10-6 mutations per gene per cell division
• a single gene will undergo mutations in
1010 occasions during a humans lifetime
Cancer is caused by a slow accumulation of
numerous random mutations in a single cell
line
Cancers develop in slow stages from mildly
aberrant cells
Cancer incidence as a function of age
Delayed onset of cancer following exposure
to 2-naphthylamine
Age adjusted cancer death rates in the U.S.
females
males
The Ames Test for Mutagenicity
Metastasis from carcinoma of the prostrate gland
Benign vs. Malignant Tumors
Melanoma cells with low filamin levels crawl
poorly and tend not to metastasize
When filamin levels are restored the cells move
normally and become highly metastatic
Filamin crosslinks actin into 3-dimensional
networks with gel-like properties
Cancer results from somatic mutations
The Philadelphia
chromosome is
associated with
one type of leukemia
Chromosomes from breast tumors may display
abnormalities in structure and number
Rb protein control of the cell cycle
The Rb protein acts as a brake in mammalian cells
Six ways of losing the remaining good copy of a
tumor suppressor gene
When proto-oncogene becomes overactive it
becomes an oncogene
Myc Gene Amplification
Mitogens stimulate G1-Cdk and G1/S-Cdk activities
Ocogene collaboration in transgenic mice
Viruses May cause Cancer
Papillomavirus causes warts and subverts the control of cell division
Pap smears
normal
abnormal
invasive
How papillomaviruses are thought to give rise to
cancer of the uterine cervix
Activation of cell proliferation by DNA tumor
virus
Sequence of genetic changes underlying the
development of a colorectal carcinoma
Each tumor will contain a different set of
mutations
Effect of ionizing radiation on normal and cancer cells