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 member of the RTK family, is an unusual RTK in that it is catalytically inactive because of amino acid substitutions of conserved residues in the catalytic domain. We show by immunohistochemistry that it is expressed in the epithelium, stroma, and blood vessels of normal tissues. Evaluation of a panel of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) was performed. H-Ryk was overexpressed in borderline and malignant ovarian tumors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observation, 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.
Katso
R M
RM
Imperial Cancer Research Fund Molecular Oncology Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Manek
S
S
Biddolph
S
S
Whittaker
R
R
Charnock
M F
MF
Wells
M
M
Ganesan
T S
TS
D016475:3T3 Cells / Q000201:enzymology* / Q000637:transplantation; D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000201:enzymology; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018291:Cystadenoma, Mucinous / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018293:Cystadenoma, Serous / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000201:enzymology; D014162:Transfection; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases