Lecture

Introduction to Molecular and Cell Biology, Biol. 220

Lecture 37: Cancer

Definition of Cancer

Cancer is a disease characterized by the uncontrolled proliferation of cells.

The normal mechanisms that regulate cellular growth and division break down.

This breakdown results from mutations that overcome the normal limits to the number of cell divisions that can take place before a cell dies.

What controls how often cells divide?

Cell cycle control

Cell Cycle

Length of telomeres

Impact of telomere on cell longivity and immortalization

Stages of Cancer progression

Primary cells

Immortalization (benign)

Transformation (cancerous)

Metastasis (systemic spread)

Stages of cancer progression Normal and Tumor cells

Which genes are most likely to cause cancer when disrupted?

Those involved in cell signalling pathways responsible for stimulation of cell division. (ligands, receptors, signal transduction components)

Mutation of Cell receptor Src mutations and transformation

Those genes that make proteins that control the cell cycle. (cyclins, tumor suppressor genes)

RB gene concentration

Those genes that induce mutations. (mutator genes, repair enzyme genes)

Mutator genes

Proto-oncogenes (genes with normal functions that when mutated can induce cancer state)

Proto-Oncogenes

Those gene that monitor DNA damage (p53)

p53 gene concentration and oncogenesis

P53 and cell cycle control

What are some causes of cancer?

Accumulation of mutations (natural accumulation, exposure to carcinogens, aging)

Cancer and aging Accumulation of mutations

Virus infections

Three mechanisms:

Virus produces an inhibitor of cell cycle control

Permissive and non-permissive cells and oncogenesis SV40 and oncogenesis

Virus picks up and carries one of the cellular proto-oncogenes

Picking up an v-onc gene

Src mutations and transformation

Virus inserts into genome next to proto-oncogene and causes overproduction.

Retroviral insertion and oncogene activation