Expression and functions of transmembrane mucin MUC13 in ovarian cancer.
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.
Chauhan
Subhash C
SC
Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, South Dakota 57105, USA. subhash.chauhan@usd.edu
Vannatta
Kelley
K
Ebeling
Mara C
MC
Vinayek
Namita
N
Watanabe
Akira
A
Pandey
Krishan K
KK
Bell
Maria C
MC
Koch
Michael D
MD
Aburatani
Hiroyuki
H
Lio
Yuhlong
Y
Jaggi
Meena
M
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
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