Genes tumor-suppressors

Harris, C., Hollstein, M. Clinical implications of the p53 tumor-suppressor gene. N. Engl. f. Med. 

In apoptotic cell death, several factors such as growth factors, NO, the tumor suppressor gene p53, and the protein encoded by this gene contribute to the process that leads to cell death. One of the functions of p53 protein is the activation of apoptosis if a cell is transformed to a malignant cell. Apoptosis typically leads to the formation of smaller membrane-encapsulated particles within the cell. Apoptotic cell death begins in the nucleus and proceeds to other parts of the cell. The death process may be quite advanced before it can... 

Nucleic acids in the DNA contain a high number of nucleophilic sites that can be attacked by electrophilic intermediates (metabolites) of chemical compounds. DNA adducts formed may cause alterations in the expression of a critical gene in the cell and thus lead to cell death. For example, modification of p53 tumor suppressor gene may inactivate the functions of the p53 protein and render cells sensitive to malignant transformation. Also, formation of RNA adducts may inhibit key cellular events because RNA is essential for protein synthesis. 

TABLE 5.22 Important Oncogenes and Tumor Suppressor Genes in Human Cancers... 

In Drosophila, Fat functions as a tumor suppressor gene and dachsous is involved in thorax, leg, and wing development. Several human and mouse homologs have been identified. FAT1 regulates actin filaments, and the Fail knockout leads to defects in glomerular slit formation [3]. 

PTEN is a phosphatase, which is a product of a tumor suppressor gene. This phosphatase has an unusual broad specificity and can remove phosphate groups attached to serine, threonine, and tyrosine residues. It is believed that its ability to dephosphorylate phosphati-dylinositol (PI) 3,4,5-triphosphate, the product of PI-3 kinase, is responsible for its tumor suppressor effects. 

TABLE 85-1. Examples of Oncogenes and Tumor-Suppressor Genes... 

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Tumor suppressor genes Genes that normally restrain cell growth, but when missing or inactivated by mutation, allow cells to grow uncontrolled and tumors to form. 

Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., and Candey, L. C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151—162. 

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