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.
Liu
Suling
S
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus 43210-1092, USA.
Kulp
Samuel K
SK
Sugimoto
Yasuro
Y
Jiang
Jiahua
J
Chang
Hsiang-Lin
HL
Lin
Young C
YC
D001940:Breast / Q000166:cytology / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology*; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic; D004848:Epithelium / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology; D014407:Tumor Cells, Cultured; D015029:Zeranol / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D004958:Estradiol; D015029:Zeranol; C516850:PTPRG protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5