Yf. Zhai et al., INCREASED EXPRESSION OF SPECIFIC PROTEIN-TYROSINE PHOSPHATASES IN HUMAN BREAST EPITHELIAL-CELLS NEOPLASTICALLY TRANSFORMED BY THE NEU ONCOGENE, Cancer research, 53(10), 1993, pp. 2272-2278
Protein tyrosine phosphorylation/dephosphorylation is a fundamental me
chanism in the regulation of cell proliferation and neoplastic transfo
rmation; this metabolic process is modulated by the opposing activitie
s of protein tyrosine kinases and protein tyrosine phosphatases (PTPas
es). While the role of protein tyrosine kinases has been examined exte
nsively in human breast tumorigenesis, the role of PTPases in this pro
cess is virtually unknown. To address this issue. an activated neu onc
ogene was introduced into an immortalized nontumorigenic human breast
epithelial cell line (184B5). This resulted in a substantial increase
in P185neu expression, which led to the formation of progressively gro
wing carcinomas after such cells were inoculated into athymic nude mic
e. Importantly, a striking increase in the expression of specific PTPa
ses, LAR and PTP1B, was observed in 3 independently neu transformed ce
ll lines and their derived tumors. This elevation was verified at both
the mRNA and protein levels. TC-PTP PTPase expression was only slight
ly increased in these neu transformed cells, and no expression of CD45
PTPase was observed. The level of neu expression, as well as the diff
erential expression between P185neu and LAR/PTP1B, directly correlated
with tumorigenicity. Furthermore, rat mammary carcinomas with elevate
d neu expression (neu-induced) also had sharply elevated LAR-PTPase ex
pression when compared to rat mammary carcinomas with little or no neu
expression (7,12-dimethylbenzanthracene induced); the level of expres
sion of LAR PTPase was directly correlated with the level of neu expre
ssion. Thus, our results provide the first evidence that, in human bre
ast carcinoma cells and in rat mammary carcinomas that have an induced
increase in neu expression, a consistent and substantial increase in
the expression of specific PTPases occurs. The relationship between P1
85neu-protein tyrosine kinase expression and specific PTPase expressio
n may play a critical role in human breast tumorigenesis.