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Differences between phosphotyrosine accumulation and Neu/ErbB‐2 receptor expression in astrocytic proliferative processes: Implications for glial oncogenesis
Author(s) -
Kristt Donald A.,
Yarden Yosef
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960915)78:6<1272::aid-cncr16>3.0.co;2-y
Subject(s) - cancer research , receptor tyrosine kinase , erbb , carcinogenesis , biology , glioma , tyrosine kinase , tyrosine phosphorylation , gliosis , signal transduction , pathology , cancer , medicine , microbiology and biotechnology , genetics
BACKGROUND Previous work has shown that enhanced growth potential of malignant astrocytomas correlates with increased expression of growth factor receptor tyrosine kinases. The functional implications of increased receptor expression were addressed by analyzing possible accumulation of phosphotyrosyl proteins in neoplastic and nonneoplastic astrocytic proliferative processes. The results were compared with the expression of Neu receptor protein (also called ErbB‐2 or HER‐2). METHODS Western immunoblots and immunocytochemistry were utilized to evaluate glioma and carcinoma cell lines, neonatal astrocytic cultures, and human brain biopsies of graded gliosis and astrocytomas. The effects of three tyrosine kinase inhibitors on 3 H‐thymidine uptake and cell proliferation and viability were examined in cultured glioma cells. RESULTS Phosphotyrosine was conspicuously elevated in all three grades of astrocytoma, but remained at low levels in nonneoplastic astrocytic proliferations. Dose‐dependent decreases in DNA synthesis and proliferation of cultured glioma cells occurred after inhibition of tyrosine kinase. Neu receptor protein showed increased expression in malignant astrocytomas (including glioblastomas) and severe reactive gliosis. CONCLUSIONS Upregulation of tyrosyl protein phosphorylation enables differentiation of neoplastic from nonneoplastic astrocytic proliferative states. Inhibition of this phosphorylation impairs growth of glioma cells. Increased Neu receptor protein expression can distinguish malignant from low grade astrocytomas. We speculate that genetic events leading to stably increased phosphotyrosine may be critical for neoplastic transformation of astrocytes, whereas increased receptor tyrosine kinase expression could be a factor in the aggressive growth associated with malignancy. Cancer 1996;78:1272‐83.