Research Focus in the Fraizer Laboratory: Cancer, Mechanisms of tumorigenesis
Dr. Fraizer’s laboratory uses molecular and genetic approaches to delineate mechanisms of tumor development. Currently the major focus is the investigation of an innovative mechanism of modulating the Androgen receptor (AR); a steroid hormone receptor that plays a central role in the development of the prostate and prostate cancer. One potential regulator of the AR signal transduction pathway is the Wilms’ tumor suppressor gene (WT1), a zinc finger transcription factor essential for early kidney and gonadal development. On-going work delineating the role of WT1 in the AR pathway began with our novel observation that WT1 binds regulatory elements within the AR promoter region and modulates AR expression. Currently research is directed towards developing a model of androgen-independent prostate cancer progression.
Fraizer GC, Shimamura R, Zhang X, Saunders GF. PAX 8 regulates human WT1 transcription through a novel DNA binding site. J Biol Chem 272:30678-30687, 1997
Shimamura R, Fraizer GC, Trapman J, Lau YfC, Saunders GF. The Wilms' tumor gene WT1 can regulate genes involved in sex determination and differentiation: SRY, Mullerian-inhibiting substance, and the androgen receptor. Clin Cancer Res 3:2571-2581, 1997
Zaia A, Fraizer G, Piantanelli L, Saunders G. Transcriptional regulation
of the androgen-signaling pathway by the Wilms' tumor suppressor gene WT1.
AntiCancer Research 21:1-10,2001