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 10 8 to 10 9 cells are present

Why doesn’t cancer happen more often? cell divisions in a human lifetime mutations per gene per cell division a single gene will undergo mutations in 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. femalesmales

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 normalabnormalinvasive

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