Involvement of breast epithelial-stromal interactions in the regulation of protein tyrosine phosphatase-γ (PTPγ) mRNA expression by estrogenically active agents
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- Liu, S., Kulp, S.K., Sugimoto, Y. et al. Breast Cancer Res Treat (2002) 71: 21. doi:10.1023/A:1013343718942
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Background. Protein tyrosine phosphatase γ (PTPγ) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicate that estradiol-17β (E2)-induced suppression of PTPγ 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. PTPγ 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 PTPγ 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 PTPγ mRNA expression by E2 and Z.
Results. PTPγ mRNA expression was lower in cancerous than in normal breast tissues. Both E2 and Z suppressed PTPγ mRNA levels in cultured normal breast tissues by ∼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 PTPγ mRNA to a greater degree in epithelial cells than in stromal cells. In whole breast tissues, PTPγ was immunolocalized to the epithelium. Treatment with E2 or Z diminished PTPγ staining indicating reductions in PTPγ at the protein level.
Conclusions. The results indicate that both E2 and Z regulate PTPγ expression in human breast and that epithelial–stromal cells interaction is important in the regulation of PTPγ expression by estrogenically active agents.