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Transformation is associated with an increase in sensitivity to TNF‐mediated lysis as a result of an increase in TNF‐induced protein tyrosine phosphatase activity
Author(s) -
Sasaki Carl Y.,
Patek Paul Q.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990331)81:1<141::aid-ijc23>3.0.co;2-v
Subject(s) - tumor necrosis factor alpha , vanadate , biology , phosphorylation , protein tyrosine phosphatase , phosphatase , tyrosine phosphorylation , lytic cycle , cell culture , microbiology and biotechnology , medicine , cancer research , endocrinology , biochemistry , immunology , genetics , virus
Using the tumor necrosis factor (TNF)‐resistant cell line B/CN and an anchorage‐independent variant, 10ME, we have shown a relationship between transformation and sensitivity to TNF. Here, we report a role for protein tyrosine phosphorylation in expression of these phenotypes. Several studies have demonstrated the involvement of protein phosphorylation in the TNF signaling pathways that leads to cell death. We show that TNF treatment of the TNF‐sensitive, transformed cells results in a marked increase in protein tyrosine phosphatase (PTP) activity and a decrease in protein tyrosine kinase (PTK) activity. In contrast, TNF treatment of the TNF‐resistant, non‐transformed parental cells results in a marked increase in PTK activity. Also, the PTP inhibitors vanadate and bromotetramisole decrease TNF lytic activity, indicating that the PTP activity observed is an integral part of the lytic process. Treatment of targets with vanadate prior to TNF exposure had no effect on TNF‐mediated lysis. In contrast, the addition of vanadate up to 4 hr after TNF‐treatment resulted in a decrease in TNF‐mediated lysis. Our findings indicate that the phosphatase activity is induced after TNF binds its receptor. Our data also indicate that the decrease in TNF‐mediated lysis caused by PTP inhibitors is not due to the inhibition of the TNF lytic mechanism. Instead, vanadate increases a TNF resistance mechanism; it does so by blocking the PTP‐mediated inhibition of the TNF resistance mechanism. Further, the lineage relationship of these cell lines suggests that there is a biochemical relationship between anchorage‐independence, tumorigenicity and the protein tyrosine phosphorylation that governs sensitivity to TNF. Int. J. Cancer 81:141–147, 1999. © 1999 Wiley‐Liss, Inc.