Abstract
AMP-activated protein kinase (AMPK) plays a central role in regulating energy metabolism in cells. AMPK activation results in down-regulation of anabolic pathways (e.g., fatty acid biosynthesis) and switches on catabolic processes such as glucose uptake, glycolysis or fatty acid oxidation. Recent studies in cell culture models have shown that the growth of tumor cell lines was inhibited by AMPK activation, but the expression of AMPK in human ovarian tumors has not been reported so far. In this study we investigated AMPK expression in a cohort of 70 ovarian carcinomas, 14 borderline tumors and 5 normal ovaries and linked the protein expression data to Gas chromatography/time of flight mass spectrometry (GC/TOF-MS) based metabolomics. We observed a significantly higher expression in ovarian carcinomas compared to borderline tumors and normal ovaries (p=0.038). Decreased AMPK expression correlated significantly with higher tumor grade (p=0.009) and was of adverse prognosis in patients with advanced tumor stages (p=0.016) as well as in patients with serous ovarian carcinomas (p=0.037). GC/TOF-MS based metabolomics revealed a significantly higher concentration of glucose in AMPK-negative carcinomas (p=0.022) as well as overexpression of other metabolites from carbohydrate metabolism. Our results indicate a role for AMPK in progression of ovarian tumors and point towards a prognostic impact of AMPK expression for patient overall survival. Furthermore, our data suggest a deregulation of the AMPK-dependent energy metabolism in human ovarian carcinomas. In future clinical studies, activation of AMPK in ovarian carcinoma patients with advanced tumor stages might be an interesting therapeutic approach.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1005-1012 |
| Number of pages | 8 |
| Journal | Oncology Reports |
| Volume | 25 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2011 |
Fingerprint
Keywords
- AMP-activated protein kinase
- Energy metabolism
- Immunohistochemistry
- Metabolomics
- Ovarian carcinoma
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Prognostic impact of AMP-activated protein kinase expression in ovarian carcinoma : Correlation of protein expression and GC/TOF-MS-based metabolomics. / Buckendahl, Ann Christin; Budczies, Jan; Fiehn, Oliver; Darb-Esfahani, Silvia; Kind, Tobias; Noske, Aurelia; Weichert, Wilko; Sehouli, Jalid; Braicu, Elena; Dietel, Manfred; Denkert, Carsten.
In: Oncology Reports, Vol. 25, No. 4, 04.2011, p. 1005-1012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prognostic impact of AMP-activated protein kinase expression in ovarian carcinoma
T2 - Correlation of protein expression and GC/TOF-MS-based metabolomics
AU - Buckendahl, Ann Christin
AU - Budczies, Jan
AU - Fiehn, Oliver
AU - Darb-Esfahani, Silvia
AU - Kind, Tobias
AU - Noske, Aurelia
AU - Weichert, Wilko
AU - Sehouli, Jalid
AU - Braicu, Elena
AU - Dietel, Manfred
AU - Denkert, Carsten
PY - 2011/4
Y1 - 2011/4
N2 - AMP-activated protein kinase (AMPK) plays a central role in regulating energy metabolism in cells. AMPK activation results in down-regulation of anabolic pathways (e.g., fatty acid biosynthesis) and switches on catabolic processes such as glucose uptake, glycolysis or fatty acid oxidation. Recent studies in cell culture models have shown that the growth of tumor cell lines was inhibited by AMPK activation, but the expression of AMPK in human ovarian tumors has not been reported so far. In this study we investigated AMPK expression in a cohort of 70 ovarian carcinomas, 14 borderline tumors and 5 normal ovaries and linked the protein expression data to Gas chromatography/time of flight mass spectrometry (GC/TOF-MS) based metabolomics. We observed a significantly higher expression in ovarian carcinomas compared to borderline tumors and normal ovaries (p=0.038). Decreased AMPK expression correlated significantly with higher tumor grade (p=0.009) and was of adverse prognosis in patients with advanced tumor stages (p=0.016) as well as in patients with serous ovarian carcinomas (p=0.037). GC/TOF-MS based metabolomics revealed a significantly higher concentration of glucose in AMPK-negative carcinomas (p=0.022) as well as overexpression of other metabolites from carbohydrate metabolism. Our results indicate a role for AMPK in progression of ovarian tumors and point towards a prognostic impact of AMPK expression for patient overall survival. Furthermore, our data suggest a deregulation of the AMPK-dependent energy metabolism in human ovarian carcinomas. In future clinical studies, activation of AMPK in ovarian carcinoma patients with advanced tumor stages might be an interesting therapeutic approach.
AB - AMP-activated protein kinase (AMPK) plays a central role in regulating energy metabolism in cells. AMPK activation results in down-regulation of anabolic pathways (e.g., fatty acid biosynthesis) and switches on catabolic processes such as glucose uptake, glycolysis or fatty acid oxidation. Recent studies in cell culture models have shown that the growth of tumor cell lines was inhibited by AMPK activation, but the expression of AMPK in human ovarian tumors has not been reported so far. In this study we investigated AMPK expression in a cohort of 70 ovarian carcinomas, 14 borderline tumors and 5 normal ovaries and linked the protein expression data to Gas chromatography/time of flight mass spectrometry (GC/TOF-MS) based metabolomics. We observed a significantly higher expression in ovarian carcinomas compared to borderline tumors and normal ovaries (p=0.038). Decreased AMPK expression correlated significantly with higher tumor grade (p=0.009) and was of adverse prognosis in patients with advanced tumor stages (p=0.016) as well as in patients with serous ovarian carcinomas (p=0.037). GC/TOF-MS based metabolomics revealed a significantly higher concentration of glucose in AMPK-negative carcinomas (p=0.022) as well as overexpression of other metabolites from carbohydrate metabolism. Our results indicate a role for AMPK in progression of ovarian tumors and point towards a prognostic impact of AMPK expression for patient overall survival. Furthermore, our data suggest a deregulation of the AMPK-dependent energy metabolism in human ovarian carcinomas. In future clinical studies, activation of AMPK in ovarian carcinoma patients with advanced tumor stages might be an interesting therapeutic approach.
KW - AMP-activated protein kinase
KW - Energy metabolism
KW - Immunohistochemistry
KW - Metabolomics
KW - Ovarian carcinoma
UR - http://www.scopus.com/inward/record.url?scp=79952215103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952215103&partnerID=8YFLogxK
U2 - 10.3892/or.2011.1162
DO - 10.3892/or.2011.1162
M3 - Article
C2 - 21271224
AN - SCOPUS:79952215103
VL - 25
SP - 1005
EP - 1012
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 4
ER -