14-3-3σ modulates pancreatic cancer cell survival and invasiveness

Divas Neupane, Murray Korc

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Purpose: The purpose of the present study was to investigate the potential role of 14-3-3a in pancreatic ductal adenocarcinoma (PDAC). Experimental Design: 14-3-3 isoform expression was determined by real-time quantitative PCR in laser capture normal pancreatic ductal cells and pancreatic cancer cells and in 5 pancreatic cancer cell lines. PANC-1 cells, with low levels of 14-3-3σ, were stably transfected with a human 14-3-3σ cDNA. Conversely, high endogenous 14-3-3σ levels inT3M4 cells were suppressed by specific short hairpin RNA. Apoptosis, motility, and invasiveness were studied. Results: The cancer cells in 7 PDAC samples expressed high levels of 14-3-3a mRNAby quantitative PCR when compared with normal pancreatic duct cells. 14-3-3σ protein levels were high in BxPC3, COLO-357, andT3M4 cells, intermediate in ASPC-1 cells, and low in PANC-1 cells. Most cell lines released detectable amount of 14-3-3σ into conditioned medium. Overexpression of 14-3-3σ in PANC-1 cells led to resistance to cisplatinum-induced apoptosis, increased basal migration, and increased invasion in response to epidermal growth factor and insulin-like growth factor-I. By contrast, short hairpin RNA-mediated knockdown of endogenous 14-3-3σ in T3M4 cells did not alter migration but led to enhanced cisplatinum sensitivity, increased invasiveness in response to epidermal growth factor, and decreased invasiveness in response to insulin-like growth factor-I. Conclusions: 14-3-3σ contributes to the chemoresistance of pancreatic cancer cells and exerts cell type-dependent effects on cell migration and invasion. Therefore, strategies aimed at suppressing 14-3-3σ expression and function may have a therapeutic benefit in subgroups of patients with PDAC.

Original languageEnglish (US)
Pages (from-to)7614-7623
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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