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Reg IV: A Promising Marker of Hormone Refractory Metastatic Prostate Cancer

Departments of ¹ Statistics and ² Urology, and the ³ Molecular Biology Institute, Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California; ⁴ Department of Pathology, Dana-Farber Cancer Institute, Harvard School of Medicine, Boston, Massachusetts; and ⁵ Department of Urology, Stanford University School of Medicine, Stanford, California

Requests for reprints: Robert E. Reiter, Department of Urology, 66-128 UCLA Center for the Health Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095. Phone: 310-794-7224; Fax: 310-206-5343; E-mail: rreiter{at}mednet.ucla.edu.

The diagnosis and management of prostate cancer is hampered by the absence of markers capable of identifying patients with metastatic disease. In order to identify potential new markers for prostate cancer, we compared gene expression signatures of matched androgen-dependent and hormone refractory prostate cancer xenografts. One candidate gene overexpressed in a hormone refractory xenograft was homologous to the regenerating protein gene family, a group of secreted proteins expressed in the gastrointestinal tract and overexpressed in inflammatory bowel disease and cancer. This gene, Reg IV, was confirmed to be differentially expressed in the LAPC-9 hormone refractory xenograft. Consistent with its up-regulation in a hormone refractory xenograft, it is expressed in several prostate tumors after neoadjuvant hormone ablation therapy. As predicted by its sequence homology, it is secreted from transiently transfected cells. It is also expressed strongly in a majority of hormone refractory metastases represented on two high-density tissue microarrays. In comparison, it is not expressed by any normal prostate specimens and only at low levels in 40% of primary tumors. These data support Reg IV as a candidate marker for hormone refractory metastatic prostate cancer.

Key Words: Prostate cancer • secreted • marker • Reg IV