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July 12, 2005

Researchers Discover How Tumor Suppressor Gene Works

Topics: Medicine

Interesting thing about this article, the moment I saw it I immediately thought about - green tea, well, at least the EGCG(Epigallocatechin-3-gallate, a green-tea polyphenol) in the tea.

A team of University of Minnesota researchers has discovered how a gene that suppresses the development of melanoma and other human cancers works. The study points the way to treatments based on the function of the gene.

A critical event in the development of melanoma and other human cancers is the inactivation of a gene known as "p16." Normally, p16 keeps cells from growing rapidly, a condition that sometimes leads to tumor formation. Working with mouse epidermis and cultured human melanoma and nonmelanoma cancer cells, the team found that p16 inactivates key enzymes -- called JNK 1 and JNK 2 -- in the process. The enzymes are normally activated by exposure to ultraviolet light. By shutting down the enzymes, p16 keeps them from activating a huge complex of proteins, which, when active, attaches to chromosomes and turns on many genes that promote cell growth.

The p16 gene works by producing a protein that attaches to the enzymes, preventing them from performing their function. When the researchers added the p16 protein to colonies of cancer cells in culture, it diminished the size of many colonies, wiping out some of them. It also decreased the total number of cancer cells.

The researchers have designed a very small protein that mimics the action of the natural p16 protein. They hope that the "small protein" will have anti-cancer activity." In testing now, a patent application on the protein has been filed. The researchers, led by Zigang Dong, director of the university's Hormel Institute in Austin, Minn., expect to see clinical trials of this or similar treatments begin in a few years. The work will be published online July 10 in the journal Nature Structural & Molecular Biology.

Suggested reading:

Data has demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. The data suggests that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network(includes p16INK4a) and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

Other suggested readings:

The genetics of susceptibility to cutaneous melanoma.

Anti-Invasive Effects of Green Tea Polyphenol
EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor
of Metallo and Serine Proteases
(tea polyphenols can activate specific cell cycle inhibitors (p21, p27, p16, p18) (Ahmad et al., 2000a) and signal transducers (MAP-K) (Chen et al., 2000).

Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells.

Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma.

Posted by Hyscience at July 12, 2005 11:34 PM



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