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Disconnect between skin cells implicated in common skin cancer

A mutation that prevents skin cells from making normal connections with each other plays an unexpectedly early and important role in the development of the skin cancer, suggests a study published in the February 23, 2001 issue of Cell.

By altering one molecule in a skin cell-cell junction in mice researchers at the University of Chicago profoundly changed the skin and caused it to behave like a pre-cancerous condition called squamous cell carcinoma in situ. Squamous cell carcinoma is one of the two most common forms of skin cancer with more than one million cases reported in the United States each year.

"Although mutations of this molecule have been found in some types of cancer, it has generally been assumed that this was a late event following other mutations disrupting cell-cycle control," said Elaine Fuchs, Ph.D., Amgen Professor of Molecular Genetics and Cell Biology and a Howard Hughes Investigator at the University of Chicago, and lead investigator of the study.

"We discovered surprisingly, this component's loss appears to be a critical early event in the development of skin cancer," said Fuchs. "This molecule appears to be doing more than simply participating in cell-cell junctions."

The organization the skin's epidermal layer depends on cell-cell connections formed by two types of intercellular structures: adherens junctions and desmosomes. The molecule alpha-catenin plays a role in adherens junctions and connects these junctions to a dynamic structural framework in the cell, the actin cytoskeleton.

Their strategy was to breed a mouse that has had the gene for alpha-catenin removed, or knocked-out, selectively in skin cells. The mouse embryo developed normally until its skin and hair begin to develop, around the 14th day of gestation. As these specialized cells, called keratinocytes, developed they did not make adherens junctions. The alpha-catenin needed to anchor the junction was missing.

Changes in the skin of the knockout mouse wer
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Contact: Jeanne Galatzer-Levy
jgalatz@uchospitals.edu
773-702-6241
University of Chicago Medical Center
22-Feb-2001


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