The Models of Action of Cancer Genes
Abstract
Early models of cancer genetics categorized cancer genes into oncogenes, which are growth inducing, and tumor suppressor genes. Cells harboring mutant p53 genes lose the ability to arrest in G1 after exposure to gamma radiation or other genotoxins. It was gathered that mice with p53 genes disruptions are completely viable, but they exhibit an enhanced rate of tumor formation and the abrogation of the G1 checkpoint after exposure to DNA-damaging agents. BRCA1 and BRCA2 are structurally unrelated genes with converging clinical effects. Disabling mutations in either gene render an individual more susceptible to breast and ovarian cancer. Although both genes carry the hallmarks of a tumor suppressor gene, their main function is not growth regulation. MLH1 and MSH2 genes are responsible for syndrome of hereditary nonpolyposis colorectal cancer. The cancer susceptibility gene, PTEN/MMAC is an example of a genetic guardian whose primary function is to regulate cell death and survival. This review has found that, PTEN, localized to 10q23, has been identified through position cloning as the gene responsible for Cowden’s syndrome.
References
O’ Connor PM. Mammalian G1 and G2 phase checkpoints. Cancer surv 1997; 29:151
O’ Connor PM, Jackman J, Bae I, et al. Characterization of the p53 tumor suppressor pathway
in cell lines of the National Cancer Institute Anticancer Drug Screen and correlations with the
growth- inhibitory potency of 123 anticancer agents. Cancer Res 1997; 57:4285
Donehower LA, Godley LA, Aldaz CM et al. The role of p53 loss in genomic instability and
tumor progression in a murine mammary cancer model. Prog Clin Biol Res 1996; 395:1
Livingstone LR, White A, Sprouse J et al. Altered cell cycle arrest and gene amplification
potential accompany loss of wildtype p53. Cell 1992; 70:923
Holt JT, Thomas ME, Szabo C, et al. Growth retardation and tumor inhibition by BRCA1. Nat
Genet 1996; 12:298
Chen J, Silver DP, Walpita D, et al. Stable interaction between the products of the BRCA1 and
BRAC2 tumor suppressor genes in mitotic and meiotic cells. Mol cell 1998; 2:317
Gowen LC, Avrutskaya AV, Latour AM, Koller BH, Leadon SA. BRCA1 required for
transcription-coupled repair of oxidative DNA damage. Science 1998; 281:1009
Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation
hypersensitivity mediated by RadS1 in mice lacking Brca2. Nature 1997; 386:804
Abbott DW, Freeman ML, Holt JT. Doubled-strand break repair deficiency and radiation
sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 1998; 90:978
Papadopoulos N, Lindblom A. Molecular basis of HNPCC: mutations of MMR genes. Hum
Mutat 1997; 10:89
Eng C. Genetics of Cowden syndrome: through the looking glass of oncology. Int J Oncol
; 12:701
Suzuki A, de la Pompa JL, Stambolic V et al. High cancer susceptibility and embryonic
lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 1998;
:1169
Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/ Akt-dependent
cell survival by the tumor suppressor. Cell 1998; 95:29
Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to
the cell-intrinsic death machinery. Cell 1997; 91:231
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Journal of 99Science
This work is licensed under a Creative Commons Attribution 4.0 International License.
All rights reserved. 99Science. 2019
