Incidence, mechanism and prognostic value of activated AKT in pancreas cancer

M. G. Schlieman, B. N. Fahy, R. Ramsamooj, Laurel A Beckett, Richard J Bold

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

When activated, the serine/threonine kinase AKT mediates an antiapoptotic signal implicated in chemoresistance of various cancers. The mechanism(s) of AKT activation are unknown, though overexpression of HER-2/neu has been implicated in breast cancer. Therefore, we determined the incidence of activated AKT in human pancreatic cancer, whether HER-2/neu is involved in AKT activation, and if AKT activation is associated with biologic behaviour. HER-2/neu expression and AKT activation were examined in seven pancreatic cancer cell lines by Western blotting. The in vitro effect of HER-2/neu inhibition on AKT activation was similarly determined. Finally, 78 pancreatic cancer specimens were examined for AKT activation and HER-2/neu overexpression, and correlated with the clinical prognostic variable of histologic grade. HER-2/neu was overexpressed in two of seven cell lines; these two cell lines demonstrated the highest level of AKT activation. Inhibition of HER-2/neu reduced AKT activation in vitro. AKT was activated in 46 out of 78 (59%) of the pancreatic cancers; HER-2/neu overexpression correlated with AKT activation (P = 0.015). Furthermore, AKT activation was correlated with higher histologic tumour grade (P = 0.047). Thus, it is concluded that AKT is frequently activated in pancreatic cancer; this antiapoptotic signal may be mediated by HER-2/neu overexpression. AKT activation is associated with tumour grade, an important prognostic factor.

Original languageEnglish (US)
Pages (from-to)2110-2115
Number of pages6
JournalBritish Journal of Cancer
Volume89
Issue number11
DOIs
StatePublished - Dec 1 2003

Keywords

  • AKT
  • HER-2/neu
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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