EXPRESSION OF THE EXTRACELLULAR-MATRIX SIGNALING MOLECULE CYR61 IS DOWN-REGULATED IN PROSTATE-CANCER

BACKGROUND. Prostate cancer (CaP) is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to id entify genes related to the development of prostate cancer. METHODS. T he RNA of 4 patients with untreated CaP was analyzed for differentiall y expressed genes. Using DD-PCR, we identified a downregulated cDNA-fr agment in these prostate cancer cells. This fragment (N7) was cloned a nd further analyzed by CMRT-PCR, Northern-blot analysis, and in situ h ybridization. RESULTS. Sequence analysis revealed that N7 is identical to the 3'-untranslated region of the recently described immediate ear ly gene Cyr61. Comparative multiplex RT-PCR with sequence specific pri mers showed that Cyr61 is downregulated in the tumor tissue of 7 out o f 13 patients. By in situ hybridization we could demonstrate that the expression of Cyr61 is restricted to the epithelium of the prostate. I mmunohistochemical analysis showed that Cyr61 protein could be found i n the epithelium of normal prostatic tissue, whereas prostate cancer t issue showed a marked decrease of Cyr61 protein expression. CONCLUSION S. Cyr61 is a member of the emerging family of extracellular signaling proteins and enhances the effect of bFGF. The changed pattern of expr ession Cyr61 might therefore contribute to the altered interactions be tween epithelial and stromal cells in prostate carcinoma. (C) 1998 Wil ey-Liss. Inc.