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Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth.

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Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Leitner, O. Sela, M. Yarden, Y. Stancovski, I. Hurwitz, E. Ullrich, A.
Description	Author Affiliation: Stancovski I ( Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.);
Abstract	The ERBB2 (also called HER2, neu, and c-erbB-2) gene product, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. An antibody directed to the rat oncogenic receptor has been previously shown to have an antitumor effect in model systems. In an attempt to extend this observation to the protooncogenic human receptor and also to understand the underlying mechanism, we generated a panel of monoclonal antibodies specific to the extracellular portion of the ERBB2 protein. The effects of the antibodies on tumor growth were compared with their cellular and biochemical actions in vitro. Surprisingly, opposing in vivo effects were observed: although some antibodies almost completely inhibited the growth in athymic mice of transfected murine fibroblasts that overexpress Erbb-2, other antibodies either accelerated tumor growth or resulted in intermediate responses. When tested on cultured human breast carcinoma cells or ERBB2 transfectants, the tumor-stimulatory antibody was found to induce significant elevation of tyrosine phosphorylation of the ERBB2 protein. In contrast, only partial correlation was observed between the capacity to restrict tumor growth and the effects of the antibodies on receptor degradation and cellular proliferation in vitro. This suggests that the antitumor antibodies affect both receptor function and host-tumor interactions. Our results may help establish experimental criteria for the selection of specific antibodies for use either alone or in conjunction with other molecules as pharmacological antitumor agents.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	88
Language	English
Publisher	National Academy of Sciences
Publisher Date	1991-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Neoplasms, Experimental Pathology Proto-Oncogene Proteins Physiology Receptors, Cell Surface Animals Antibodies, Monoclonal Cell Division Mice Mice, Nude Neoplasm Transplantation Oncogenes Phosphoproteins Metabolism Phosphotyrosine Precipitin Tests Protein-Tyrosine Kinases Receptor, ErbB-2 Tumor Cells, Cultured Tyrosine Analogs & Derivatives Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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