Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells

N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L Meza, J. F. Rodriguez-Sierra, J. P. Aubert, Surinder Kumar Batra

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4α, and a membrane-bound growth factor-like subunit, MUC4β. MUC4 mRNA contains unique 5′ and 3′ coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is comparable with that of wild-type MUC4 (930 kDa) but represents only 10% of VNTR. Stable ectopic expression of mini-MUC4 in two human pancreatic cancer cell lines, Panc1 and MiaPaCa, showed that MUC4 minigene expression follows a biosynthesis and localisation pattern similar to the wild-type MUC4. Expression of MUC4 resulted in increased growth, motility, and invasiveness of the pancreatic cancer cells in vitro. Ultra-structural examination of MUC4-transfected cells showed the presence of increased number and size of mitochondria. The MUC4-expressing cells also demonstrated an enhanced tumorigenicity in an orthotopic xenograft nude mice model, further supporting a direct role of MUC4 in inducing the cancer properties. In conclusion, our results suggest that MUC4 promotes tumorigenicity and is directly involved in growth and survival of the cancer cells.

Original languageEnglish (US)
Pages (from-to)345-357
Number of pages13
JournalBritish journal of cancer
Volume97
Issue number3
DOIs
StatePublished - Jul 31 2007

Fingerprint

Mucins
Pancreatic Neoplasms
Minisatellite Repeats
Mitochondrial Size
Growth
Heterografts
Nude Mice
Neoplasms
Cell Survival
Intercellular Signaling Peptides and Proteins
Glycoproteins
Proteins
Complementary DNA
Carcinoma
Cell Line
Messenger RNA
Membranes

Keywords

  • MUC4
  • Mitochondria
  • Mucin
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells. / Moniaux, N.; Chaturvedi, P.; Varshney, G. C.; Meza, Jane L; Rodriguez-Sierra, J. F.; Aubert, J. P.; Batra, Surinder Kumar.

In: British journal of cancer, Vol. 97, No. 3, 31.07.2007, p. 345-357.

Research output: Contribution to journalArticle

Moniaux, N. ; Chaturvedi, P. ; Varshney, G. C. ; Meza, Jane L ; Rodriguez-Sierra, J. F. ; Aubert, J. P. ; Batra, Surinder Kumar. / Human MUC4 mucin induces ultra-structural changes and tumorigenicity in pancreatic cancer cells. In: British journal of cancer. 2007 ; Vol. 97, No. 3. pp. 345-357.
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