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© The Rockefeller University Press, 0021-9525/1997//935 $5.00
The Journal of Cell Biology, Volume 136, Number 4, , 1997 935-944

Article

Growth-inhibitory Activity and Downregulation of the Class II Tumor-suppressor Gene H-rev107 in Tumor Cell Lines and Experimental Tumors



Christine Sers*,{ddagger}, Urban Emmenegger*, Knut Husmann*, Katharina Bucher*, Ann-Catherine Andres§, and Reinhold Schäfer*,{ddagger}

* Division of Cancer Research, Department of Pathology, University of Zürich, CH-8091 Zürich, Switzerland; {ddagger} Institute of Pathology, University Hospital Charite, D-10729 Berlin, Germany; and § Division of Clinical and Experimental Research, University of Berne, CH-3004 Berne, Switzerland

The H-rev107 gene is a new class II tumor suppressor, as defined by its reversible downregulation and growth-inhibiting capacity in HRAS transformed cell lines. Overexpression of the H-rev107 cDNA in HRAS-transformed ANR4 hepatoma cells or in FE-8 fibroblasts resulted in 75% reduction of colony formation. Cell populations of H-rev107 transfectants showed an attenuated tumor formation in nude mice. Cells explanted from tumors or maintained in cell culture for an extended period of time no longer exhibited detectable levels of the H-rev107 protein, suggesting strong selection against H-rev107 expression in vitro and in vivo. Expression of the truncated form of H-rev107 lacking the COOH-terminal membrane associated domain of 25 amino acids, had a weaker inhibitory effect on proliferation in vitro and was unable to attenuate tumor growth in nude mice. The H-rev107 mRNA is expressed in most adult rat tissues, and immunohistochemical analysis showed expression of the protein in differentiated epithelial cells of stomach, of colon and small intestine, in kidney, bladder, esophagus, and in tracheal and bronchial epithelium. H-rev107 gene transcription is downregulated in rat cell lines derived from liver, kidney, and pancreatic tumors and also in experimental mammary tumors expressing a RAS transgene. In colon carcinoma cell lines only minute amounts of protein were detectable. Thus, downregulation of H-rev107 expression may occur at the level of mRNA or protein.

Please address correspondence to Christine Sers, Institute of Pathology, Charité, Humboldt University Berlin, Schumannstr. 20/21, D-10117 Berlin, Germany. Tel.: (49) 30-2802-5181. Fax.: (49) 30-2802-8206. E-mail: chsers{at}rz.charite.hu-berlin.de


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