December 31, 2003
SickKids researchers determine the protein Gli2 is a key regulator controlling cell proliferation in the epidermis
Researchers at The Hospital for Sick Children (SickKids) and the University of Toronto (U of T) have determined that the protein Gli2 is a key regulator controlling cell proliferation in the epidermis (the outer layer of skin). This supports the group’s past findings that Gli2 can function abnormally as a cancer-inducing gene in the adult skin. The researchers have also determined that Gli2 plays a pivotal role in hair development. This research is reported in the January 15 issue of the scientific journal Genes & Development.
Non-melanoma skin cancer is the most prevalent malignancy in humans. The incidence of non-melanoma skin cancer is increasing in North America and accounts for 40 per cent of all cancers. In Canada, around 70,000 people are diagnosed with skin cancer each year. A major cause of these cancers is due to abnormal activation of a genetic pathway known as the Sonic hedgehog (Shh) signaling pathway. Shh plays a critical role in hair follicle development and skin cancer but how it affects these processes remains unclear. This study has shown that the Gli2 protein serves as a key messenger in the Shh signaling pathway and functions as a master regulator of cell proliferation in the epidermis.
“A complex process involving both epidermis and dermis (the inner layer of the skin) is required for hair growth. In the absence of Gli2, mice will not develop hair. Strikingly, we found that hair growth is restored by simply repairing Gli2 function in the epidermis,” said Pleasantine Mill, lead author of the study, and a U of T graduate student.
“The finding that Gli2 controls cell proliferation in the skin and hair growth is exciting because it provides important insights into how abnormal activation of the Shh pathway results in skin cancer. Future studies in this area may also lead to treatments for common skin disorders, including hair loss,” said Dr. Chi-chung Hui, the study’s principal investigator, a SickKids senior scientist and an associate professor of Molecular and Medical Genetics at U of T.
Other members of the research team are: Drs. Peter Kim, Rong Mo, and Hong Fu, all from SickKids, and Drs. Marina Grachtchouk and Andrzej Dlugosz from the University of Michigan Comprehensive Cancer Center.
This research was supported by the National Cancer Institute of Canada, Canadian Institutes of Health Research, Natural Sciences & Engineering Research Council of Canada, National Institutes of Health, and The Hospital for Sick Children Foundation. Abstract »»