Involvement of breast epithelial-stromal interactions in the regulation of protein tyrosine phosphatase-γ (PTPγ) mRNA expression by estrogenically active agents

Background. Protein tyrosine phosphatase gamma (PTP gamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicate that estradiol-17 beta (E-2)-induced suppression of PTP gamma may play a role in mammary tumorigenesis. Zeranol (Z), a nonsteroidal growth promoter with estrogenic activity that is used by the US meat industry, induces estrogenic responses in primary cultured breast cells and breast cancer cell lines. Methods. PTP gamma mRNA expression in human breast tissues and cells isolated from surgical specimens of mammoplasty and breast cancer patients were detected and quantified by RT-PCR. Immunohistochemical staining was used to localize PTP gamma in human breast tissues. Breast epithelial and stromal cells were isolated and co-cultured to determine the involvement of cell-cell interaction in the regulation of PTP gamma mRNA expression by E-2 and Z. Results. PTP gamma mRNA expression was lower in cancerous than in normal breast tissues. Both E-2 and Z suppressed PTP gamma mRNA levels in cultured normal breast tissues by similar to 80%, but had a lesser effect in cultured epithelial cells isolated from normal breast tissues. In the co-culture system, both E-2 and Z suppressed PTP gamma mRNA to a greater degree in epithelial cells than in stromal cells. In whole breast tissues, PTP gamma was immunolocalized to the epithelium. Treatment with E-2 or Z diminished PTP gamma staining indicating reductions in PTP gamma at the protein level. Conclusions. The results indicate that both E-2 and Z regulate PTP gamma expression in human breast and that epithelial-stromal cells interaction is important in the regulation of PTP gamma expression by estrogenically active agents.