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

[BACKGROUND] Protein tyrosine phosphatase gamma (PTPgamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicate that estradiol-17beta (E2)-induced suppression of PTPgamma 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] PTPgamma 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 PTPgamma 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 PTPgamma mRNA expression by E2 and Z.

[RESULTS] PTPgamma mRNA expression was lower in cancerous than in normal breast tissues. Both E2 and Z suppressed PTPgamma mRNA levels in cultured normal breast tissues by approximately 80%, but had a lesser effect in cultured epithelial cells isolated from normal breast tissues. In the co-culture system, both E2 and Z suppressed PTPgamma mRNA to a greater degree in epithelial cells than in stromal cells. In whole breast tissues, PTPgamma was immunolocalized to the epithelium. Treatment with E2 or Z diminished PTPgamma staining indicating reductions in PTPgamma at the protein level.

[CONCLUSIONS] The results indicate that both E2 and Z regulate PTPgamma expression in human breast and that epithelial-stromal cells interaction is important in the regulation of PTPgamma expression by estrogenically active agents.