Prostate cancer kills approximately 30,000 men in the United States each year. Like many cancers, prostate cancer can often be treated successfully if it is diagnosed at an early stage. However, the standard treatment, surgery to remove the prostate and nearby lymph nodes, can result in impotence or incontinence. Therapeutics that treat prostate tumors with minimal side effects are needed.

The glioma-associated (GLI) proteins may provide a new drug target for cancer treatment. These proteins are a family of transcription factors involved in the activation of the highly conserved Hedgehog (Hh) signaling pathway in mammals. In particular, Gli2 appears to be the major nuclear effector of Hh signaling. Because activation of this pathway in adult tissues has been implicated in tumorigenesis, agents that inhibit Gli2 may reduce tumor growth.

UW-Madison researchers have developed a method of treating prostate cancer by inhibiting the expression of Gli2. Reducing the amount of Gli2 protein down-regulates the Hh signaling pathway and decreases tumor growth.

A short hairpin RNA, or shRNA, is a small RNA sequence that can be used to inhibit gene expression. The inventors developed a lentiviral-based shRNA that specifically inhibits the expression of Gli2. By selectively inhibiting Gli2, they were able to reduce the growth of prostate cancer cells in vivo and in vitro.

 

File Number: P08215US 

Other Information:
Thiyagarajan S., Bhatia N., Reagan-Shaw S., Cozma D., Thomas-Tikhonenko A., Ahmad N. and Spiegelman V.S. 2008. Role of GLI2 Transcription Factor in Growth and Tumorigenicity of Prostate Cells. Cancer Res. 67, 10642-10646.