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

Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ - Br. J. Cancer (2003)

Bottom Line: The in vitro effect of HER-2/neu inhibition on AKT activation was similarly determined.Inhibition of HER-2/neu reduced AKT activation in vitro.AKT activation is associated with tumour grade, an important prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA.

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.

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Representative IHC staining for phospho-AKT in pancreatic tumours: (A) tumour without detectable expression and (B) tumour with strong expression of phospho-AKT consistent with activation of AKT. Normal pancreatic ducts do not have detectable phospho-AKT (× 40, original magnification).
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fig4: Representative IHC staining for phospho-AKT in pancreatic tumours: (A) tumour without detectable expression and (B) tumour with strong expression of phospho-AKT consistent with activation of AKT. Normal pancreatic ducts do not have detectable phospho-AKT (× 40, original magnification).

Mentions: We noted that 51 of the 78 tumours (65%) demonstrated HER-2/neu overexpression by immunohistochemistry (Figure 4Figure 4


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

Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ - Br. J. Cancer (2003)

Representative IHC staining for phospho-AKT in pancreatic tumours: (A) tumour without detectable expression and (B) tumour with strong expression of phospho-AKT consistent with activation of AKT. Normal pancreatic ducts do not have detectable phospho-AKT (× 40, original magnification).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376856&req=5

fig4: Representative IHC staining for phospho-AKT in pancreatic tumours: (A) tumour without detectable expression and (B) tumour with strong expression of phospho-AKT consistent with activation of AKT. Normal pancreatic ducts do not have detectable phospho-AKT (× 40, original magnification).
Mentions: We noted that 51 of the 78 tumours (65%) demonstrated HER-2/neu overexpression by immunohistochemistry (Figure 4Figure 4

Bottom Line: The in vitro effect of HER-2/neu inhibition on AKT activation was similarly determined.Inhibition of HER-2/neu reduced AKT activation in vitro.AKT activation is associated with tumour grade, an important prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA.

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.

Show MeSH
Related in: MedlinePlus