title: Expression and functions of transmembrane mucin MUC13 in ovarian cancer.
abstract: MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH(2) kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P < 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer.
authors.affiliation: Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, South Dakota 57105, USA. subhash.chauhan@usd.edu
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: Kelley
authors.initials: K
authors.lastname: Vannatta
authors.forename: Mara C
authors.initials: MC
authors.lastname: Ebeling
authors.forename: Namita
authors.initials: N
authors.lastname: Vinayek
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Krishan K
authors.initials: KK
authors.lastname: Pandey
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bell
authors.forename: Michael D
authors.initials: MD
authors.lastname: Koch
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Yuhlong
authors.initials: Y
authors.lastname: Lio
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D002449:Cell Aggregation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous; D015854:Up-Regulation; D054462:p21-Activated Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D048670:MAP Kinase Kinase 4; D009077:Mucins; D018719:Erb-b2 Receptor Tyrosine Kinases; D054462:p21-Activated Kinases; C429552:MUC13 protein, human; C515903:PAK1 protein, human