Function analysis of estrogenically regulated protein tyrosine phosphatase gamma (PTPgamma) in human breast cancer cell line MCF-7.
Protein tyrosine phosphatase gamma (PTPgamma) is a member of the receptor-like family of tyrosine phosphatases and has been implicated as a tumor suppressor gene in kidney and lung cancers. Based on our previous findings, we hypothesize that PTPgamma is a potential estrogen-regulated tumor suppressor gene in human breast cancer. To examine the effects of PTPgamma on growth of MCF-7 human breast cancer cells and compare the estrogenic responses of human breast cells with different PTPgamma expression levels, we established several stably transfected MCF-7 cell lines expressing different levels of PTPgamma, which were confirmed by RT-PCR and immunostaining. In our work, we used the antisense construct to breakdown endogenous PTPgamma level in MCF-7 cells. The results from doubling time assay suggested that PTPgamma is capable of inhibiting MCF-7 breast cancer cell growth. We further demonstrated that PTPgamma is able to inhibit anchorage-independent growth of breast cancer cells in soft agar and reduce the estrogenic responses of MCF-7 cell proliferation to estradiol-17beta (E(2)) and zeranol (Z, a nonsteroidal growth promoter with estrogenic activity). Our data suggest that PTPgamma may function as an important modulator in regulating the process of tumorigenesis in human breast.
Liu
Suling
S
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Sugimoto
Yasuro
Y
Sorio
Claudio
C
Tecchio
Cristina
C
Lin
Young C
YC
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011995:Recombination, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015029:Zeranol / Q000494:pharmacology
D017931:DNA Primers; D004968:Estrogens, Non-Steroidal; D009419:Nerve Tissue Proteins; D004958:Estradiol; D015029:Zeranol; C516850:PTPRG protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5