TY - JOUR
T1 - Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma
T2 - Implications for tumor progression and clinical outcome
AU - Witkiewicz, Agnieszka K.
AU - Nguyen, Katherine H.
AU - Dasgupta, Abhijit
AU - Kennedy, Eugene P.
AU - Yeo, Charles J.
AU - Lisanti, Michael P.
AU - Brody, Jonathan R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - Pancreatic cancer is a devastating disease that afflicts over 35,000 Americans every year. Since therapeutic options are limited, understanding the molecular aspects of this disease is critical for moving towards targeted treatment of this aggressive form of cancer. Caveolin-1 (Cav-1) and fatty acid synthase (FASN) are two proteins that have been shown to be dysregulated in a number of cancers. Functionally these proteins have been shown to be involved in the process of tumorigenesis. We thus surveyed the expression of both these critical proteins in a series of pancreatic precancerous lesions (pancreatic intraepithelial neoplasia, PanIN) and pancreatic cancers. Cav-1 and FASN expression correlated predominantly with clinical characteristics, such as histologic grade and advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor differentiation status) and a significant survival advantage was found in patients with low co-expressing FASN and Cav-1 tumors. Cav-1 and FASN expression was absent in PanIN lesions and the normal ducts and acini. Of note, Cav-1 expression was detected in the fibroblasts of the desmoplastic pancreatic cancer stroma, but not in stromal cells of the normal pancreas. Mechanistically, these data support the notion that these proteins are co-regulated either directly or indirectly by another factor. Importantly, the co-expression of these proteins significantly correlates with clinical features and survival status of pancreatic cancer patients. Thus, Cav-1 and FASN may functionally cooperate in the process of pancreatic tumorigenesis, and as such, may be good candidate prognostic markers and targets for therapeutic intervention.
AB - Pancreatic cancer is a devastating disease that afflicts over 35,000 Americans every year. Since therapeutic options are limited, understanding the molecular aspects of this disease is critical for moving towards targeted treatment of this aggressive form of cancer. Caveolin-1 (Cav-1) and fatty acid synthase (FASN) are two proteins that have been shown to be dysregulated in a number of cancers. Functionally these proteins have been shown to be involved in the process of tumorigenesis. We thus surveyed the expression of both these critical proteins in a series of pancreatic precancerous lesions (pancreatic intraepithelial neoplasia, PanIN) and pancreatic cancers. Cav-1 and FASN expression correlated predominantly with clinical characteristics, such as histologic grade and advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor differentiation status) and a significant survival advantage was found in patients with low co-expressing FASN and Cav-1 tumors. Cav-1 and FASN expression was absent in PanIN lesions and the normal ducts and acini. Of note, Cav-1 expression was detected in the fibroblasts of the desmoplastic pancreatic cancer stroma, but not in stromal cells of the normal pancreas. Mechanistically, these data support the notion that these proteins are co-regulated either directly or indirectly by another factor. Importantly, the co-expression of these proteins significantly correlates with clinical features and survival status of pancreatic cancer patients. Thus, Cav-1 and FASN may functionally cooperate in the process of pancreatic tumorigenesis, and as such, may be good candidate prognostic markers and targets for therapeutic intervention.
KW - Caveolin-1
KW - Fatty acid synthase
KW - Pancreatic cancer
KW - Pancreatic ductal adenocarcinoma
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U2 - 10.4161/cc.7.19.6719
DO - 10.4161/cc.7.19.6719
M3 - Article
C2 - 18802406
AN - SCOPUS:53649086945
SN - 1538-4101
VL - 7
SP - 3021
EP - 3025
JO - Cell Cycle
JF - Cell Cycle
IS - 19
ER -