Tumor suppressor gene

A tumor suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. A mutation or deletion of such a gene will increase the probability of the formation of a tumor.

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Two-hit hypothesis

Unlike oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis,' which implies that both alleles that code for a particular gene must be affected before an effect is manifested. This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein. In other words, tumor suppressors are usually not haploinsufficient, although there are notable exceptions (the p53 gene product).

Functions

Tumor suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both. The functions of tumor suppressor proteins fall into several categories including the following:^[1]

1. Repression of genes that are essential for the continuing of the cell cycle. If these genes are not expressed, the cell cycle will not continue, effectively inhibiting cell division.
2. Coupling the cell cycle to DNA damage. As long as there is damaged DNA in the cell, it should not divide. If the damage can be repaired, the cell cycle can continue.
3. If the damage can not be repaired, the cell should initiate apoptosis, or programmed cell death, to remove the threat it poses for the greater good of the organism.
4. Some proteins involved in cell adhesion prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit metastasis. These proteins are known as metastasis suppressors.^{[2] [3]}

Examples

The first tumor suppressor protein discovered was the pRb protein in human retinoblastoma; however, recent evidence has also implicated pRb as a tumor survival factor.

Another important tumor suppressor is the p53 tumor suppressor protein produced by the TP53 gene.

PTEN acts by opposing the action of PI3K, which is essential for anti-apoptotic, pro-tumorogenic Akt activation.

See also

• Metastasis suppressor
• Adenomatosis polyposis coli
• Oncogene
• Cancer
• DNA repair
• Signal transduction
• Von Hippel Lindau Binding protein 1

References

1. ^ Sherr C (2004). "Principles of tumor suppression". Cell 116 (2): 235-46. PMID 14744434.
2. ^ Yoshida, BA, Sokoloff, MM, Welch, DR, Rinker-Schaeffer CW. 2000. Metastasis-suppressor genes: a review and perspective on an emerging field. Journal of the National Cancer Institute 92: 1717-1730.
3. ^ Hirohashi S, Kanai Y (2003). "Cell adhesion system and human cancer morphogenesis". Cancer Sci 94 (7): 575-81. PMID 12841864.