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

• Published in: British journal of cancer Vol. 89; no. 11; pp. 2110 - 2115
• Main Authors: Schlieman, M G, Fahy, B N, Ramsamooj, R, Beckett, L, Bold, R J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2003
• Subjects: Adenocarcinoma - enzymology; Antibodies, Monoclonal - pharmacology; Apoptosis; Breast cancer; Cancer research; Chemotherapy; Enzyme Activation; Humans; Medical prognosis; Medical research; Molecular and Cellular Pathology; Pancreatic cancer; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - pathology; Prognosis; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2 - immunology; Receptor, ErbB-2 - metabolism; Receptor, ErbB-2 - physiology; Tumor Cells, Cultured; Tumors; Sacramento California; United States > US; California
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6601396

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.