LAR-PTPASE CDNA TRANSFECTION SUPPRESSION OF TUMOR-GROWTH OF NEU ONCOGENE-TRANSFORMED HUMAN BREAST-CARCINOMA CELLS

The incidence of amplification of neu oncogene-encoded protein tyrosin e kinase in human breast cancer strongly supports the concept that pro tein tyrosine phosphorylation and dephosphorylation are key regulatory mechanisms in the proliferation, differentiation, and neoplastic tran sformation of breast epithelial cells. We examined the potential regul atory role of protein tyrosine phosphatases (PTPases) in the maintenan ce of cellular tyrosine phosphorylation by the introduction of leukocy te com mon-antigen-related PTPase (LAR-PTPase) cDNA into a tumorigenic human breast carcinoma cell line that overexpressed p185(neu) protein tyrosine kinase. The transfected human breast carcinoma cells express ed elevated levels of LAR-PTPase as assessed by reverse transcription- polymerase chain reaction and by analysis of LAR-PTPase protein. The L AR-PTPase-transfected human breast carcinoma cells had a significantly (P<0.01) slower proliferation rate in vitro than control-transfected cells. When LAR-PTPase-transfected cells were inoculated into athymic nude mice, a consistent and significant (P<0.05) suppression of tumor growth was observed. These results provide evidence that a specific PT Pase, LAR-PTPase, can play a suppressive regulatory role in the tumor growth of human breast carcinoma cells that overexpress p185(neu) prot ein tyrosine kinase. (C) 1995 Wiley-Liss, Inc.