CH 24 Genetics

Cancer stem cell hypothesis

tumor cells that do proliferate give rise to cancer stem cells that have capacity for self renewal

Driver mutations

give growth advantage to tumor cells

Passenger mutations

no direct contribution to cancer phenotype

Mutator phenotype

high level of genomic instability

Signal transduction

initiates program of gene expression that propels cell out of G0 and into cell cycle

Cyclins

bind to CDK triggering cyclin CDK complex

Cyclin CDK complex

advances cell through cycle

Apoptosis

programmed cell death

Apoptosis steps

fragment nuclear envelope, disrupt internal structures, dissolution of cell into apoptotic bodies, engulfing of bodies by phagocytic cell

Caspases

initating apoptosis

Bcl2 and BAX

control caspases

Tumor suppressors

genes whose products regulate cell cycle check points or initate apoptosis

Oncogene

proto-oncogene that is mutated and contributes to the development of cancer

ras genes

encode signal transduction molecules that are associated with cell membrane and regulate cell growth and division

oncogene products

growth factors, GTP binding proteins, protein kinases, transcription factors

Photo oncogenes

promote cellular growth

Proteolytic enzymes

high levels in malignant tumors

Retroviruses cause cancer

proviral DNA integrates near oncogene, some viruses carry oncogenes

Non acutely transforming

acquire v-onc gene by recombination

Acutely transforming retroviruses

have v-onc gene at time of infection

v-onc gene

stimulates growth

Hpv

DNA virus that can transform cells proteins that degrade or block tumor suppressors

Tumror suppressors associated with cancer in recessive manner