Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line

Karl G. Kohlgraf, Andrew J. Gawron, Michiyo Higashi, Jane L Meza, Michael D. Burdick, Shinichi Kitajima, David Lee Kelly, Thomas C. Caffrey, Michael A Hollingsworth

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

MUC1 is a polymorphic, highly glycosylated, type I transmembrane protein expressed by ductal epithelial cells of many organs including pancreas, breast, gastrointestinal tract, and airway. MUC1 is overexpressed and differentially glycosylated by adenocarcinomas that arise in these organs, and is believed to contribute to invasive and metastatic potential by contributing to cell surface adhesion properties [via the tandem repeat (TR) domain] and through morphogenetic signal transduction [via the cytoplasmic tail (CT)]. The large extracellular TR of MUC1 consists of a heavily glycosylated, 20 amino acid sequence that shows allelic variation with respect to number of repeats. This portion of MUC1 may directly mediate adhesive or antiadhesive interactions with other surface molecules on adjacent cells and through these interactions initiate signal transduction pathways that are transmitted through the CT. We investigated the contribution of the TR domain and the CT of MUC1 to the in vivo invasive and metastatic potential, and the gene expression profile of the human pancreatic tumor cell line S2-013. Results showed that S2-013 cells overexpressing full-length MUC1 displayed a less invasive and metastatic phenotype compared with control-transfected cells and cells expressing MUC1 lacking the TR domain or CT. Clonal populations were analyzed by cDNA array gene expression analysis, which showed differences in the gene expression profiles between the different cell lines. Among the genes differentially expressed were several that encode proteins believed to play a role in invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)5011-5020
Number of pages10
JournalCancer Research
Volume63
Issue number16
StatePublished - Aug 15 2003

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Tandem Repeat Sequences
Pancreatic Neoplasms
Tail
Cell Line
Transcriptome
Signal Transduction
Surface Properties
Oligonucleotide Array Sequence Analysis
Tumor Cell Line
Cell Adhesion
Cell Communication
Adhesives
Gastrointestinal Tract
Pancreas
Amino Acid Sequence
Proteins
Adenocarcinoma
Breast
Epithelial Cells
Neoplasm Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. / Kohlgraf, Karl G.; Gawron, Andrew J.; Higashi, Michiyo; Meza, Jane L; Burdick, Michael D.; Kitajima, Shinichi; Kelly, David Lee; Caffrey, Thomas C.; Hollingsworth, Michael A.

In: Cancer Research, Vol. 63, No. 16, 15.08.2003, p. 5011-5020.

Research output: Contribution to journalArticle

Kohlgraf, Karl G. ; Gawron, Andrew J. ; Higashi, Michiyo ; Meza, Jane L ; Burdick, Michael D. ; Kitajima, Shinichi ; Kelly, David Lee ; Caffrey, Thomas C. ; Hollingsworth, Michael A. / Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. In: Cancer Research. 2003 ; Vol. 63, No. 16. pp. 5011-5020.
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AU - Burdick, Michael D.

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