Abstract:
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 epithelial-stromal signaling in pancreatic desmoplasia and may serve as diagnostic or therapeutic targets.
journal_name
Pancreasjournal_title
Pancreasauthors
Binkley CE,Zhang L,Greenson JK,Giordano TJ,Kuick R,Misek D,Hanash S,Logsdon CD,Simeone DMdoi
10.1097/00006676-200411000-00003subject
Has Abstractpub_date
2004-11-01 00:00:00pages
254-63issue
4eissn
0885-3177issn
1536-4828pii
00006676-200411000-00003journal_volume
29pub_type
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