Lynda Chin, MD, and her colleagues found that they could increase both the number of tumors and the speed with which they formed by exposing newborn mice with an intact Rb pathway to UV radiation. (A pathway is a chain of biochemical signals that regulates cellular activity.) Those mice in which the Rb pathway was already essentially knocked out were unaffected by the dose of UV radiation. "It looks like the Rb pathway is specifically targeted by ultraviolet radiation," said Chin, the study's senior author. Karupiah Kannan, PhD, and Norman Sharpless, MD, formerly at the DFCI, are first authors on the study.
Melanoma is the deadliest form of skin cancer and, left unchecked, can spread aggressively to other parts of the body. However, if caught early, many melanoma lesions can be effectively treated surgically. The discovery that UV radiation triggers melanoma formation by dismantling a specific pathway inside the skin's pigment-producing cells, or melanocytes, offers the possibility of an efficient means of distinguishing, at an early stage, cancerous moles from non-cancerous ones.
"If you see in a sun-induced lesion that its Rb pathway has been inactivated, then the risk of it becoming a melanoma is much greater than one without such a lesion," said Chin, who is also an assistant professor of dermatology at Harvard Medical School. "You could then use that as a prognostic factor to determine which of these
Contact: Bill Schaller
Dana-Farber Cancer Institute