title: Identification and characterization of membralin, a novel tumor-associated gene, in ovarian carcinoma.
abstract: Identification of new genes in cancer is the key to understand the molecular basis of tumor development as well as provide potential diagnostic markers and therapeutic targets. A novel gene, membralin (GeneBank accession number: DQ005958), was cloned from a human ovarian cancer cell line. Human membralin is unique and does not share significant sequence homology with other human genes, only membralins of other species. The gene contains 11 exons which encode at least two spliced variants in human cancer. The long form of membralin (membralin-1) comprises all 11 exons, encoding a protein of 620-amino acids long and the short form of membralin (membralin-3) contains all exons except for exon 10, encoding a protein of 408 amino acids. Expression of different membralin isoforms depends on tissue type. The long form, membralin-1, is expressed in ovarian and colorectal carcinomas but not in breast or pancreatic carcinomas, which express only the short splice form, membralin-3. Membralin-1-GFP fusion protein demonstrates exclusive cytoplasmic localization. Based on quantitative real-time PCR, in situ hybridization and Western blot analysis, membralin was highly expressed in ovarian serous carcinomas as compared to ovarian surface epithelium (P<0.001). Ovarian carcinomas in effusions demonstrated a significantly higher level of membralin expression than in solid tumors (P<0.001). In conclusion, these findings represent the first characterization of human membralin and suggest that membralin is a novel tumor-associated marker in ovarian serous carcinomas.
authors.affiliation: Department of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Chen
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Cheng
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Robert L
authors.initials: RL
authors.lastname: Giuntoli
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C475036:TMEM259 protein, human