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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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Related in: MedlinePlus

Time-dependent decrease in phospho-AKT following inhibition of HER-2/neu with trastuzamab (30 μg ml)−1 in MIA-PaCa-2 (A) or PANC-1 (B) pancreatic cancer cells. Inhibition was observed following 30 min of treatment and returned to baseline after 2 h of treatment. AKT levels are shown for equivalency of loading. Data of densitometric quantification of protein levels are shown below each lane (phospho-AKT normalised to AKT level).
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fig2: Time-dependent decrease in phospho-AKT following inhibition of HER-2/neu with trastuzamab (30 μg ml)−1 in MIA-PaCa-2 (A) or PANC-1 (B) pancreatic cancer cells. Inhibition was observed following 30 min of treatment and returned to baseline after 2 h of treatment. AKT levels are shown for equivalency of loading. Data of densitometric quantification of protein levels are shown below each lane (phospho-AKT normalised to AKT level).

Mentions: To determine the functional coupling of HER-2/neu to AKT activation, the MIA-PaCa-2 and PANC-1 cell lines were treated with the neutralising/blocking monoclonal anti-HER-2/neu antibody trastuzamab (Herceptin®). MIA-PaCa-2 cells demonstrated a time-dependent decrease in pAKT, beginning at 30 min and terminating after 2 h of treatment (Figure 2Figure 2


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)

Time-dependent decrease in phospho-AKT following inhibition of HER-2/neu with trastuzamab (30 μg ml)−1 in MIA-PaCa-2 (A) or PANC-1 (B) pancreatic cancer cells. Inhibition was observed following 30 min of treatment and returned to baseline after 2 h of treatment. AKT levels are shown for equivalency of loading. Data of densitometric quantification of protein levels are shown below each lane (phospho-AKT normalised to AKT level).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Time-dependent decrease in phospho-AKT following inhibition of HER-2/neu with trastuzamab (30 μg ml)−1 in MIA-PaCa-2 (A) or PANC-1 (B) pancreatic cancer cells. Inhibition was observed following 30 min of treatment and returned to baseline after 2 h of treatment. AKT levels are shown for equivalency of loading. Data of densitometric quantification of protein levels are shown below each lane (phospho-AKT normalised to AKT level).
Mentions: To determine the functional coupling of HER-2/neu to AKT activation, the MIA-PaCa-2 and PANC-1 cell lines were treated with the neutralising/blocking monoclonal anti-HER-2/neu antibody trastuzamab (Herceptin®). MIA-PaCa-2 cells demonstrated a time-dependent decrease in pAKT, beginning at 30 min and terminating after 2 h of treatment (Figure 2Figure 2

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