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