Tumor Suppressor Genes

Cell cycle checkpoints

Regulatory points in the cell cycle that control progression

Tumor suppressor genes

Genes that inhibit cell growth and proliferation

Knudson's two hit hypothesis

Both alleles of a tumor suppressor gene must be mutated for loss of function

Genetic mechanisms for Tumor Suppressor Gene inactivation

Mutations in the gene itself

Epigenetic mechanisms for Tumor Suppressor Gene inactivation

Changes in gene expression without altering the DNA sequence

p53

Tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis

Rb

Tumor suppressor gene that stops cell cycle progression from G1 to S phase

BRCA

Tumor suppressor gene involved in DNA repair and genome integrity

APC

Tumor suppressor gene that negatively regulates beta-catenin activity

NF-1

Tumor suppressor gene that inactivates the RAS proto-oncogene

MDM2

Protein that regulates the degradation of p53

p21

Protein that inhibits cyclin-dependent kinases and stops cell cycle progression

ARF

Protein that sequesters MDM2 and allows p53 to trigger cell cycle arrest

APC and WNT

Influence the development of familial adenomatous polyposis and affect beta-catenin levels and transcription for cancer development

Retinoblastoma

Tumor suppressor gene that shuts down the cell cycle at G1/S and prevents replication

RB gene

Gene that is inactivated in retinoblastoma and leads to uncontrolled cell growth

E2F

Protein that is released when RB is phosphorylated, leading to transcription and cell proliferation

Li-Fraumeni syndrome

Inherited p53 mutation that predisposes individuals to malignant tumors

TP53

Gene that encodes the protein p53, the most frequently mutated gene in human cancers

Neurofibromatosis Type I

Familial cancer syndrome caused by a mutation in the NF1 gene

BRCA1

Tumor suppressor gene associated with hereditary and sporadic breast cancer

BRCA2

Tumor suppressor gene associated with hereditary and sporadic breast cancer

TGF-beta

Growth-inhibitory signal that prevents phosphorylation of pRB and blocks cell cycle progression

Retinoblastoma gene

Gene that is mutated in retinoblastoma and leads to the development of multiple tumors

APC gene

Gene that is mutated in familial adenomatous polyposis and leads to continuous activation of beta-catenin

NF-1 gene

Gene that is mutated in neurofibromatosis type I and leads to inappropriate growth and tumor formation

Hereditary breast cancer

Breast cancer caused by mutations in the BRCA1 and BRCA2 genes

TGF-Beta

Growth-inhibitory signal that is inactivated in variety of carcinomas

Inherited Cancer Syndromes

Autosomal dominant syndromes associated with an increased risk of developing cancer