( tion of Bcl-3 that is the problem Fäs...)Gene first linked to rare disease may trigger skin cancer, other tumors

"In animals deficient for CYLD, much too much Bcl-3 makes it into the nucleus where it activates genes leading to the growth of tumors."

In normal skin cells, chemical treatment or UV light prompts the transport of CYLD out into the cytoplasm, they reported. Once there, the protein binds and modifies the cancer promoter Bcl-3 to prevent its nuclear accumulation.

In addition to elucidating the cause of cylindromas, the findings might have important implications for understanding the events underlying skin cancer, and perhaps also tumors in other body tissues, the researchers said.

Indeed, the group noticed an intriguing trend--most of the tumors found in the mutant mice developed from cells of the epidermis rather than the hair-follicle cells thought to be involved in cylindromatosis. They therefore conducted a preliminary analysis of CYLD levels in human skin cancers originating from the epidermis, including basal cell carcinomas (BCC) and squamous cell carcinomas (SCC).

BCC and SCC represent the two most common forms of skin cancer, which together affect an estimated one million Americans each year.

"Interestingly, we observed reduced or absent expression of CYLD in more than ten samples of BCC and SCC, respectively," the researchers wrote. "This strongly suggests that CYLD plays a general role as a tumor suppressor, which is in agreement with its ubiquitous expression pattern and with a recent observation showing that CYLD levels are downregulated in several other tumors such as kidney, liver, and uterine cervix."

The researchers are now further examining their CYLD-deficient mice to find out whether the animals also show an increased prevalence of
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Source:Cell Press