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Submitted on September 8, 2004
Accepted on January 20, 2005
Cancer Center, Criss III, Room 352, Creighton University, 2500 California Plaza, Omaha, Nebraska 68178; Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030; Department of Pathology, Creighton University Medical Center, Creighton University, 601 N. 30St., Omaha, NE 68131
* To whom correspondence should be addressed. E-mail: znawaz{at}creighton.edu.
The E6-associated protein (E6-AP) is a dual function protein. It acts as an E3 ubiquitin-protein ligase as well as a steroid hormone receptors (SHRs) coactivator. Considering the influence of SHRs and their coactivators in the normal development and tumorigenesis of reproductive organs of both genders, we examined the roles of E6-AP in the tumorigenesis of breast and prostate tissues. We demonstrated that the expression of E6-AP protein is decreased in human invasive breast and prostate carcinomas compared with their adjacent normal tissues, and this downregulation of E6-AP is accompanied by the up-regulation of estrogen receptor-
(ER) in breast and androgen receptor (AR) in prostate carcinomas. Furthermore, our in vivo data from E6-AP knockout animals indicated that the expression levels of ER and AR are increased in E6-AP null mammary and prostate glands compared with that of normal control animals suggesting that E6-AP modulates the protein levels of ER and AR in breast and prostate glands.
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