Expression and functions of transmembrane mucin MUC13 in ovarian cancer

Subhash Chauhan, Kelley Vannatta, Mara C. Ebeling, Namita Vinayek, Akira Watanabe, Krishan K. Pandey, Maria C. Bell, Michael D. Koch, Hiroyuki Aburatani, Yuhlong Lio, Meena Jaggi

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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 NH2 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.

Original languageEnglish (US)
Pages (from-to)765-774
Number of pages10
JournalCancer Research
Volume69
Issue number3
DOIs
StatePublished - Feb 1 2009

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Mucins
Ovarian Neoplasms
p21-Activated Kinases
Heterografts
Cell Adhesion
Colonic Neoplasms
Small Interfering RNA
Stomach Neoplasms
Cell Movement
Ovary
Carcinogenesis
Phosphotransferases
Up-Regulation
Epithelium
Clone Cells
Immunohistochemistry
Monoclonal Antibodies
Cell Proliferation
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Expression and functions of transmembrane mucin MUC13 in ovarian cancer. / Chauhan, Subhash; Vannatta, Kelley; Ebeling, Mara C.; Vinayek, Namita; Watanabe, Akira; Pandey, Krishan K.; Bell, Maria C.; Koch, Michael D.; Aburatani, Hiroyuki; Lio, Yuhlong; Jaggi, Meena.

In: Cancer Research, Vol. 69, No. 3, 01.02.2009, p. 765-774.

Research output: Contribution to journalArticle

Chauhan, S, Vannatta, K, Ebeling, MC, Vinayek, N, Watanabe, A, Pandey, KK, Bell, MC, Koch, MD, Aburatani, H, Lio, Y & Jaggi, M 2009, 'Expression and functions of transmembrane mucin MUC13 in ovarian cancer', Cancer Research, vol. 69, no. 3, pp. 765-774. https://doi.org/10.1158/0008-5472.CAN-08-0587
Chauhan S, Vannatta K, Ebeling MC, Vinayek N, Watanabe A, Pandey KK et al. Expression and functions of transmembrane mucin MUC13 in ovarian cancer. Cancer Research. 2009 Feb 1;69(3):765-774. https://doi.org/10.1158/0008-5472.CAN-08-0587
Chauhan, Subhash ; Vannatta, Kelley ; Ebeling, Mara C. ; Vinayek, Namita ; Watanabe, Akira ; Pandey, Krishan K. ; Bell, Maria C. ; Koch, Michael D. ; Aburatani, Hiroyuki ; Lio, Yuhlong ; Jaggi, Meena. / Expression and functions of transmembrane mucin MUC13 in ovarian cancer. In: Cancer Research. 2009 ; Vol. 69, No. 3. pp. 765-774.
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