As a first step towards elucidating the role that pro-
protein convertases play in the growth regulation of
breast cancer, we studied the gene expression of 6 known human convertase members (PC1/PC3, PC2,
furin/PACE, PACE4,
PC5/
PC6 and PC7/LPC) in human
breast cancer tumors and cell lines. PC1,
furin, PACE4 and PC7 mRNAs were detected by
reverse transcriptase-polymerase chain reaction (RT-PCR) amplification in all 7 human
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 quantities of
estrogen and
progesterone receptors were assayed for
furin, PACE4 and PC1 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 found between the levels of
steroid receptors and the expression of human
furin, PCI and PC7 genes. Convertase
mRNA levels appeared similar in both the
estrogen-responsive and -unresponsive
breast cancer cell lines. Also,
proprotein convertase mRNAs were not detected in 9 histologically normal human breast tissues. These results suggest that elevated expression of some members of the pro-
protein convertase gene family is a characteristic of human
breast cancer, an event which may be important for human breast
tumorigenesis.