17 beta-estradiol-regulated expression of protein tyrosine phosphatase gamma gene in cultured human normal breast and breast cancer cells

Background: Protein tyrosine phosphatase gamma (PTP gamma) has been implica ted as a potential tumor suppressor gene in kidney and lung adenocarcinomas . We have previously shown that PTP gamma mRNA expression levels are lower in DES-induced kidney tumors than in normal kidneys of Syrian hamsters. The goals of the present study were to determine if PTP gamma mRNA is present in both normal and cancerous human breast cells, and to investigate the est rogenic regulation of PTP gamma mRNA expression in these cell types. Method s: Primary cultured human breast cells derived fram surgical specimens of m ammoplasty and breast cancer patients, as well as human breast cancer cell lines were used for the study. RT-PCR and RNase protection assay was utiliz ed to detect and quantify levels of PTP gamma mRNA among the cell types use d and between control and 17 beta-estradiol (E-2)-treated cells. Transient transfection of human estrogen receptor (ER) into MDA-MB-231 human breast c ancer cells was performed to establish the role of ER in the regulation of PTP gamma mRNA expression. Results: The results show that PTP gamma mRNA is expressed in primary cultured human breast cells isolated from mammoplasty and breast cancer patients, as well as in human cancer cell lines, and tha t E-2 significantly inhibits PTP gamma expression in ER-positive human brea st cancer cells via an ER-mediated mechanism. We show that PTP gamma mRNA l evels are lower in human breast cancel cells than in normal human breast ce lls. Furthermore, we report that PTPgamma mRNA expression is inhibited by E 2 in a dose-dependent manner in primary cultured breast cells. After treatm ent with 20 nM E2 for 24 hours, PTP gamma mRNA was significantly suppressed in primary cultured cancerous and non-cancerous cells fr om breast cancer patients, as well as in the ER-positive MCF-7 cell line by 50%, 85% and 66% , respectively. In contrast, the PTP gamma mRNA expression levels did not c hange in similarly heated ER-negative MDA-MB-231 cells. Sensitivity to E-2- induced suppression could be restored (94% inhibition) by transfecting MDA- MB-231 cells with an EA expression plasmid Conclusions: Our results are the first to suggest that PTP gamma is a potential estrogen-regulated tumor su ppressor gene in human breast cancer which may play an important role in ne oplastic processes of human breast epithelium.