Identification of L1CAM, Jagged2 and Neuromedin U as ovarian cancer-associated antigens.
In order to identify tumor-associated genes of ovarian carcinoma, we have investigated the transcriptional profile of 11 ovarian tumor cell lines and 2 immortalized ovarian surface epithelial cell lines (IOSE) derived from normal ovarian epithelium with Affymetrix GeneChip technology. We have analyzed the expression profile of 12652 genes. A total of 136 genes were up-regulated and 165 were down-regulated in at least 7 out of 11 ovarian tumor cell lines in comparison to the transcriptional profile of the IOSE cell lines with a change factor of +/-2 as the threshold level. We have focused on up-regulated genes encoding for transmembrane receptors and secreted proteins as possible markers for diagnosis and targets for therapy of ovarian carcinoma. We have identified the transmembrane Notch ligand Jagged2, cell adhesion molecule L1CAM and the secreted polypeptide Neuromedin U as possible candidates. Immunohistochemical analysis revealed expression of L1CAM predominantly in ovarian carcinomas, in borderline tumors to a lesser extent, and very rarely in ovarian non-epithelial types of cancer. Further analysis of L1CAM revealed that a splice variant lacking exons 2 and 27 is predominantly expressed in ovarian carcinoma cell lines DW and GG. Functional investigation of stable Delta(2,27)L1CAM transfectants of the ovarian tumor cell line OV-MZ-2 revealed significantly stronger adhesion to laminin in comparison to mock transfectants.
Euer
Nicole I
NI
Roche Diagnostics GmbH, Pharma Research, Im Nonnenwald 2, D-82372 Penzberg, Germany.
Kaul
Sepp
S
Deissler
Helmut
H
Möbus
Volker J
VJ
Zeillinger
Robert
R
Weidle
Ulrich H
UH
D002277:Carcinoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D000072101:Jagged-2 Protein; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis / Q000096:biosynthesis*; D009479:Neuropeptides / Q000032:analysis / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; C056900:neuromedin U