MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms

A. P. Singh, S. C. Chauhan, M. Andrianifahanana, N. Moniaux, Jane L Meza, M. C. Copin, I. Van Seuningen, Michael A Hollingsworth, J. P. Aubert, Surinder Kumar Batra

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

MUC4 mucin is a high molecular weight transmembrane glycoprotein that plays important roles in tumour biology. It is aberrantly expressed in pancreatic adenocarcinoma, while not being detectable in the normal pancreas. Previous studies have demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is defective in CF, is implicated in multiple cellular functions, including gene regulation. In the present study, using a CFTR-defective pancreatic cancer cell line and its derived subline expressing functional CFTR, we report that MUC4 expression is negatively regulated by CFTR. Short-interfering RNA (siRNA)-mediated silencing of CFTR also leads to an increased expression of MUC4. Additionally, our results suggest that CFTR-mediated regulation of MUC4 is cell density-dependent and is achieved by transcriptional and posttranslational mechanisms. Moreover, in a panel of pancreatic cancer cell lines and normal pancreas, we observed that CFTR was downregulated in pancreatic cancer cells and negatively correlated with MUC4 in most cases. An aberrant expression of MUC4 was also detected in the CF pancreas. Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in pancreatic tumour biology and suggest the implication of new signalling pathway(s) in MUC4 regulation.

Original languageEnglish (US)
Pages (from-to)30-41
Number of pages12
JournalOncogene
Volume26
Issue number1
DOIs
StatePublished - Jan 4 2007

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Adenocarcinoma
Pancreatic Neoplasms
Pancreas
Mucins
Down-Regulation
Cell Line
Neoplasms
Chloride Channels
RNA Interference
Small Interfering RNA
Glycoproteins
Cell Count
Molecular Weight

Keywords

  • CFTR
  • MUC4
  • Pancreatic adenocarcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms. / Singh, A. P.; Chauhan, S. C.; Andrianifahanana, M.; Moniaux, N.; Meza, Jane L; Copin, M. C.; Van Seuningen, I.; Hollingsworth, Michael A; Aubert, J. P.; Batra, Surinder Kumar.

In: Oncogene, Vol. 26, No. 1, 04.01.2007, p. 30-41.

Research output: Contribution to journalArticle

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