PRO-PROTEIN CONVERTASE GENE-EXPRESSION IN HUMAN BREAST-CANCER

As a first step towards elucidating the role that pro-protein converta ses play in the growth regulation of breast cancer, we studied the gen e expression of 6 known human convertase members (PCl/PC3, PC2, furin/ PACE, PACE4, PC5/PC6 and PC7/LPC) in human breast cancer tumors and ce ll lines. PCl, furin, PACE4 and PC7 mRNAs were detected by reverse tra nscriptase-polymerase chain reaction (RT-PCR) amplification in all 7 h uman breast cancer cell lines and 30 breast tumor tissues tested. PC5 expression was detected in 2/30 tumor tissues. PC2 mRNA, however, was not detected. In situ hybridization localized furin mRNA to the tumor cells; adjacent fibrous stroma and blood vessel elements were negative for furin gene expression. Thirty breast tumors with varying quantiti es of estrogen and progesterone receptors were assayed for furin, PACE 4 and PCI mRNAs by quantitative RT-PCR, and 22 tumors were assayed for PC7 mRNA. An apparent association was observed only between PACE4 and estrogen receptors. No statistically significant correlation was foun d between the levels of steroid receptors and the expression of human furin, PCI and PC7 genes. Convertase mRNA levels appeared similar in b oth the estrogen-responsive and -unresponsive breast cancer cell lines . Also, pro-protein convertase mRNAs were not detected in 9 histologic ally normal human breast tissues. These results suggest that elevated expression of some members of the pro-protein convertase gene family i s a characteristic of human breast cancer, an event which may be impor tant for human breast tumorigenesis. (C) 1997 Wiley-Liss, Inc.