UCSF and Stanford University researchers have developed genetically engineered mice that are prone to a common skin cancer. They hope the new mice models will lead to more studies aimed at developing treatments for the cancer.

The genetically altered mice developed signs of the skin cancer as a result of a single mutation, suggesting that this particular cancer may be somewhat easier to conquer than other forms of the disease, said Ervin Epstein, Jr., MD, UCSF professor of dermatology at the UCSF-affiliated San Francisco General Hospital and a senior author on the study reported in the May 2 issue of the journal Science. The mutation was located along the same biological pathway identified by the researchers last year as the genetic source of the disease.

"This is another step in calling attention to this particular signaling pathway. I think it gives us further hope that it doesn't take a lot of mutations to cause basal cell carcinoma and gives us even more confidence that if we could manipulate this pathway, we could get rid of these tumors," Epstein said.In June 1996, the UCSF and Stanford labs reported isolating the gene for basal cell carcinoma, which affects about 750,000 people in the United States a year. These tumors are not fatal and rarely spread throughout the body. They are generally treated with surgery or radiation.

In the earlier study, the researchers identified the source of the cancer in a gene known as patched. Patched acts in opposition to another gene called Sonic Hedgehog, which controls cell growth and development. The Hedgehog signaling protein binds to the patched protein and inactivates it. The result is basal cell carcinoma.

In the latest study, the researchers approached the issue further up this biological pathway by altering the Hedgehog gene so that it would produce too much of the Hedgehog protein. They reasoned that this change in Hedgehog would create the same effect as the inactivation of the patched gene and lead to basal cell carcinoma. Their experiments proved them right.

The researchers say they now hope the mouse model will prove useful in helping to develop therapies for treating human skin cancer. Though the transgenic mice die too early for prolonged study, it may be possible to modify them so that they survive long enough to be valuable research tools, the scientists reported.

1st appeared 5/5/97