Enhanced expression of 14-3-3sigma in pancreatic cancer and its role in cell cycle regulation and apoptosis

Ahmed Guweidhi, Jörg Kleeff, Nathalia Giese, Jamael El Fitori, Knut Ketterer, Thomas Giese, Markus W. Büchler, Murray Korc, Helmut Friess

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62 Scopus citations

Abstract

14-3-3sigma belongs to the 14-3-3 family of proteins, which are involved in the modulation of diverse signal transduction pathways. Loss of 14-3-3sigma expression has been observed in a number of human cancers, suggesting that it may have a role as a tumor suppressor gene. The aim of the study was to investigate the expression and the functional role of 14-3-3sigma in pancreatic ductal adenocarcinoma (PDAC). Expression of 14-3-3sigma was analyzed using laser capture microdissection (LCM), quantitative real-time-PCR (QRT-PCR), DNA arrays, immunohistochemistry and western blot analysis. The role of 14-3-3sigma in apoptosis and cell cycle regulation was evaluated by western blotting, immunoprecipitation and FACS analysis. By QRT-PCR, 14-3-3sigma mRNA levels were 54-fold increased in pancreatic adenocarcinoma in comparison with normal pancreatic samples and localized in pancreatic cancer cells as determined by LCM. In pancreatic cancer cells, the degree of 14-3-3sigma expression was not decisive for the maintenance of G2/M cell cycle check-point or induction of apoptosis. Responses to radiation or apoptosis-inducing agents were neither accompanied by a significant 14-3-3sigma accumulation nor by a change in association of 14-3-3sigma with cdc2, bad and bax. In conclusion, the marked over-expression of 14-3-3sigma in PADC together with multiple known genetic and epigenetic alterations of potential 14-3-3sigma interacting partners suggests an important role of aberrant 14-3-3sigma down-stream signaling in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1575-1585
Number of pages11
JournalCarcinogenesis
Volume25
Issue number9
DOIs
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Cancer Research

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    Guweidhi, A., Kleeff, J., Giese, N., El Fitori, J., Ketterer, K., Giese, T., Büchler, M. W., Korc, M., & Friess, H. (2004). Enhanced expression of 14-3-3sigma in pancreatic cancer and its role in cell cycle regulation and apoptosis. Carcinogenesis, 25(9), 1575-1585. https://doi.org/10.1093/carcin/bgh159