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Pinning down a cancer threesome

Studying mice with skin cancer, researchers at the Swiss Institute for Experimental Cancer Research (ISREC) and EPFL (Ecole Polytechnique Federale de Lausanne) have identified a three-way signaling pathway directly involved in tumor development. Their research, published in the August 1, 2006 issue of Genes and Development, pins down a process that could potentially be manipulated to inhibit the growth of existing carcinomas.

Genetic mutations in our cells accumulate as we age, and carcinomas are associated with alterations in certain key genes, known as tumor suppressor genes and oncogenes. The overexpression of oncogenes disrupts complex cellular signaling pathways and leads to tumor development. However, most oncogenes also play a variety of essential roles in the normal function of a cell. It is extremely difficult to pinpoint the interplay of genetic and cellular events that goes awry when a cell becomes cancerous.

To better understand the intertwined roles of three genes known to be implicated in skin cancer, Professor Andreas Trumpp and PhD student Thordur Oskarsson studied mice that carried a mutated form of one of them, the oncogene Ras. They then genetically engineered mice whose skin cells also lacked another oncogene, c-myc. The c-myc gene is known to be a master regulator in the cell, responsible for controlling several hundred other genes.

Their first surprise was that the mice without the c-myc gene in their skin cells didn't suffer any adverse effects. Unexpectedly, epidermal cells do not require c-myc for survival, normal differentiation or cellular division. However, even more surprising was that these same mice were completely resistant to developing skin cancer, even though they carried the mutated Ras gene, known to drive tumor development. As expected, mice in the control group carrying a normal copy of the c-myc gene developed cancer.

A piece of the puzzle was clearly missing. The researchers found this in
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Contact: Andreas Trumpp
andreas.trumpp@epfl.ch
41-21-692-5817
Ecole Polytechnique Fdrale de Lausanne
31-Jul-2006


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