TY - JOUR
T1 - The molecular basis of pancreatic fibrosis
T2 - Common stromal gene expression in chronic pancreatitis and pancreatic adenocarcinoma
AU - Binkley, Charles E.
AU - Zhang, Lizhi
AU - Greenson, Joel K.
AU - Giordano, Thomas J.
AU - Kuick, Rork
AU - Misek, Dave
AU - Hanash, Samir
AU - Logsdon, Craig D.
AU - Simeone, Diane M.
PY - 2004/11
Y1 - 2004/11
N2 - Objectives: Tissue desmoplasia occurs in a number of disease states, but its molecular basis is poorly understood. To determine which genes are overexpressed in cells contained within the desmoplastic stroma of pancreatic adenocarcinoma and chronic pancreatitis, we undertook genetic profiling of microdissected tissue samples of pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. We observed that samples of both pancreatic adenocarcinoma and chronic pancreatitis showed elevated expression of many shared genes compared with the normal pancreas. We hypothesized that these common genes likely important in stromal production and/or function could be identified using a strategy that involved comparisons between pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. Methods: We performed oligonucleotide microarray analysis of 6800 different genes expressed in 10 samples of pancreatic adenocarcinoma, 5 samples of normal pancreas, 5 samples of chronic pancreatitis, and 7 pancreatic cancer cell lines. Microarray findings were validated with RT-PCR, and immunohistochemistry was used to verify protein localization to the stromal compartment of both pancreatic cancer and chronic pancreatitis. Results: We employed a deductive comparison whereby genes expressed in the normal pancreas and pancreatic cancer cell lines were selectively eliminated from those expressed in common by pancreatic adenocarcinoma and chronic pancreatitis. This strategy identified 107 genes predicted to be expressed within cells of the stromal compartment of both pancreatic adenocarcinoma and chronic pancreatitis. Conclusions: These genes are likely important factors in epithelialstromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.
AB - Objectives: Tissue desmoplasia occurs in a number of disease states, but its molecular basis is poorly understood. To determine which genes are overexpressed in cells contained within the desmoplastic stroma of pancreatic adenocarcinoma and chronic pancreatitis, we undertook genetic profiling of microdissected tissue samples of pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. We observed that samples of both pancreatic adenocarcinoma and chronic pancreatitis showed elevated expression of many shared genes compared with the normal pancreas. We hypothesized that these common genes likely important in stromal production and/or function could be identified using a strategy that involved comparisons between pancreatic adenocarcinoma, chronic pancreatitis, normal pancreas, and pancreatic cancer cell lines. Methods: We performed oligonucleotide microarray analysis of 6800 different genes expressed in 10 samples of pancreatic adenocarcinoma, 5 samples of normal pancreas, 5 samples of chronic pancreatitis, and 7 pancreatic cancer cell lines. Microarray findings were validated with RT-PCR, and immunohistochemistry was used to verify protein localization to the stromal compartment of both pancreatic cancer and chronic pancreatitis. Results: We employed a deductive comparison whereby genes expressed in the normal pancreas and pancreatic cancer cell lines were selectively eliminated from those expressed in common by pancreatic adenocarcinoma and chronic pancreatitis. This strategy identified 107 genes predicted to be expressed within cells of the stromal compartment of both pancreatic adenocarcinoma and chronic pancreatitis. Conclusions: These genes are likely important factors in epithelialstromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.
KW - Gene expression
KW - Pancreatic adenocarcinoma
KW - Stroma
UR - http://www.scopus.com/inward/record.url?scp=13644257727&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13644257727&partnerID=8YFLogxK
U2 - 10.1097/00006676-200411000-00003
DO - 10.1097/00006676-200411000-00003
M3 - Article
C2 - 15502640
AN - SCOPUS:13644257727
SN - 0885-3177
VL - 29
SP - 254
EP - 263
JO - Pancreas
JF - Pancreas
IS - 4
ER -