Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: Correlation with up-regulation in epithelial ovarian cancer

Abnormalities in the function of receptor tyrosine kinases (RTKs) have been demonstrated to be important in the pathogenesis of cancer. H-Ryk, a new m ember of the RTK family, is an unusual RTK in that it is catalytically inac tive because of amino acid substitutions of conserved residues in the catal ytic domain. We show by immunohistochemistry that it is expressed in the ep ithelium, stroma, and blood vessels of normal tissues, Evaluation of a pane l of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) w as performed. H-Ryk was overexpressed in borderline and malignant ovarian t umors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observatio n, overexpression of H-Ryk in the mouse fibroblast cell line NIH3T3 induces anchorage-independent growth and tumorigenicity in nude mice. This implies that overexpression of the receptor can be transforming and may therefore be significant in the pathogenesis of ovarian cancer.