Yf. Zhai et al., LAR-PTPASE CDNA TRANSFECTION SUPPRESSION OF TUMOR-GROWTH OF NEU ONCOGENE-TRANSFORMED HUMAN BREAST-CARCINOMA CELLS, Molecular carcinogenesis, 14(2), 1995, pp. 103-110
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.