Abstract: A model system for screening and identification of compounds that interfere with Gli2 dependent tumorigenesis and provide potential use as anticancer agents is provided. In particular, the invention includes a Gli2 protein having an S662A point mutation that interferes with binding by the ubiquitin-ligase ?-TrCP. The mutation inhibits Gli2 degradation by the ubiquitin pathway. Gli2 stability and half-life are increased in the host cell resulting in an increase in Gli2-dependent transcription and concomitant neoplasia and tumorigenesis. Expression of the Gli2 mutant allows for the high throughput screening of compounds that interfere with the tumorigenesis thereby identifying anticancer agents.

Abstract: Methods and materials for reducing expression of GLI2 are disclosed including nucleic acid molecules such as short hairpin RNAs that direct cleavage of GLI2 encoding transcripts and the use of such molecules for reducing prostate cancer cell growth.

Abstract: A model system for screening and identification of compounds that interfere with Gli2 dependent tumorigenesis and provide potential use as anticancer agents is provided. In particular, the invention includes a Gli2 protein having an S662A point mutation that interferes with binding by the ubiquitin-ligase ?-TrCP. The mutation inhibits Gli2 degradation by the ubiquitin pathway. Gli2 stability and half-life are increased in the host cell resulting in an increase in Gli2-dependent transcription and concomitant neoplasia and tumorigenesis. Expression of the Gli2 mutant allows for the high throughput screening of compounds that interfere with the tumorigenesis thereby identifying anticancer agents.