RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells

Hideaki Tsutsumida, Benjamin J Swanson, Pankaj Singh, Thomas C. Caffrey, Shinichi Kitajima, Masamichi Goto, Suguru Yonezawa, Michael A Hollingsworth

Research output: Contribution to journalArticle

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Abstract

MUC1 is a highly glycosylated, type I transmembrane protein expressed by normal ductal epithelial cells of the pancreas, breast, lung, and gastrointestinal tract, and overexpressed in many cases of adenocarcinoma. We down-regulated MUC1 expression by RNA interference and investigated the effects on malignant and metastatic potential of a human pancreatic cancer cell line, S2-013. MUC1-suppressed clones, S2-013.MTII.C1 and S2-013. MTII.C2, were established by targeting a sequence 3,151 bp from the initiation codon and characterized in vitro for proliferation, invasion, and adhesion. We evaluated the effects of MUC1 suppression in vivo on tumor growth and metastatic properties following implantation into the cecum or pancreas of athymic mice. MUC1-suppressed clones showed significantly decreased proliferation in vitro and in vivo. Global gene expression was evaluated by oligonucleotide microarray analysis. Surprisingly, genes predicted to increase doubling times (cyclin B1 and cyclin D3) were overexpressed in MUC1-suppressed clones. There were alterations in expression of several genes that may affect the malignant properties of pancreatic cancer. Adhesion of MUC1-suppressed cells in vitro to type IV collagen and fibronectin was slightly increased, and adhesion was slightly decreased to type I collagen and laminin. Results of implantation to cecum and pancreas showed significant reduction of metastasis to lymph nodes, lung, or peritoneal sites compared with S2-013.gfp-neo control cells. These results support the hypothesis that MUC1 contributes significantly to growth and metastasis, and that down-regulation of MUC1 protein expression decreases the metastatic potential of pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)2976-2987
Number of pages12
JournalClinical Cancer Research
Volume12
Issue number10
DOIs
StatePublished - May 15 2006

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RNA Interference
Pancreatic Neoplasms
Pancreas
Cecum
Clone Cells
Phenotype
Adenocarcinoma
Growth
Cyclin D3
Neoplasm Metastasis
Cyclin B1
Gene Expression
Lung
Collagen Type IV
Initiator Codon
Laminin
Microarray Analysis
Collagen Type I
Oligonucleotide Array Sequence Analysis
Fibronectins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. / Tsutsumida, Hideaki; Swanson, Benjamin J; Singh, Pankaj; Caffrey, Thomas C.; Kitajima, Shinichi; Goto, Masamichi; Yonezawa, Suguru; Hollingsworth, Michael A.

In: Clinical Cancer Research, Vol. 12, No. 10, 15.05.2006, p. 2976-2987.

Research output: Contribution to journalArticle

Tsutsumida, Hideaki ; Swanson, Benjamin J ; Singh, Pankaj ; Caffrey, Thomas C. ; Kitajima, Shinichi ; Goto, Masamichi ; Yonezawa, Suguru ; Hollingsworth, Michael A. / RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 10. pp. 2976-2987.
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