Abstract
To investigate c-met expression during early pancreatic carcinogenesis. We used 46 bulk tissues and 36 micro-dissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real-time reverse transcription-polymerase chain reaction. In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues. c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microdissected pancreatic cancer cells and pancreatitis-affected epithelial cells than in normal ductal epithelial cells (both, P < 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells. Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.
MeSH Terms
Biomarkers, Tumor/analysis
Cell Line, Tumor
Cell Transformation, Neoplastic
Cells, Cultured
DNA, Neoplasm/analysis,genetics
Disease Progression
Epithelial Cells/chemistry,cytology,pathology
Fibroblasts/chemistry,cytology,pathology
Gene Expression Regulation, Neoplastic
Humans
Pancreatic Neoplasms/chemistry,genetics,pathology,physiopathology
Pancreatitis, Chronic/genetics,pathology,physiopathology
Precancerous Conditions/chemistry,genetics,pathology,physiopathology
Proto-Oncogene Proteins c-met/metabolism
RNA, Messenger/analysis,genetics
Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Biomarkers, Tumor
DNA, Neoplasm
RNA, Messenger
Proto-Oncogene Proteins c-met
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Yu Jun
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ohuchida Kenoki
Mizumoto Kazuhiro
Ishikawa Nami
Ogura Yasuhiro
Yamada Daisuke
Egami Takuya
Fujita Hayato
Ohashi Seiji
Nagai Eishi
Tanaka Masao
References (31)
31 references, click to expand
-
A new molecular biology approach in morphology: basic method and application of laser microdissection.
Med Electron Microsc. 2004 Jun;37(2):82-8
PMID: 15221649
-
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal Biochem. 1987 Apr;162(1):156-9
PMID: 2440339
-
Biosynthesis of the protein encoded by the c-met proto-oncogene.
Oncogene. 1989 Nov;4(11):1383-8
PMID: 2554238
-
Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.
N Engl J Med. 1993 May 20;328(20):1433-7
PMID: 8479461
-
Aberrant expression of c-met mRNA in human gastric carcinomas.
Int J Cancer. 1993 Aug 19;55(1):72-5
PMID: 8344755
-
The hepatocyte growth factor and its receptor.
Stem Cells. 1993 Jul;11 Suppl 2:22-30
PMID: 8401259
-
Pancreatitis is a risk factor for pancreatic cancer.
Gastroenterology. 1995 Jul;109(1):247-51
PMID: 7797022
-
Hepatocyte growth factor and Met receptor expression in human pancreatic carcinogenesis.
Am J Pathol. 1995 Oct;147(4):889-95
PMID: 7573364
-
Emerging multipotent aspects of hepatocyte growth factor.
J Biochem. 1996 Apr;119(4):591-600
PMID: 8743556
-
Analysis of K-ras oncogene mutations in chronic pancreatitis with ductal hyperplasia.
Surgery. 1997 Jan;121(1):42-9
PMID: 9001550
-
Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma.
Hepatology. 1997 Mar;25(3):619-23
PMID: 9049208
-
c-met expression in pancreatic cancer and effects of hepatocyte growth factor on pancreatic cancer cell growth.
Pancreas. 1997 Jul;15(1):35-40
PMID: 9211490
-
The risk of pancreatic cancer following pancreatitis: an association due to confounding?
Gastroenterology. 1997 Aug;113(2):587-92
PMID: 9247480
-
Tumor angiogenesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma.
Cancer. 1998 Feb 1;82(3):520-30
PMID: 9452270
-
Japan Pancreatic Cancer Registry: current status.
Pancreas. 1998 Apr;16(3):238-42
PMID: 9548661
-
Expression of c-met is a strong independent prognostic factor in breast carcinoma.
Cancer. 1998 Apr 15;82(8):1513-20
PMID: 9554529
-
Cancer statistics, 2005.
CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30
PMID: 15661684
-
MET and MYC cooperate in mammary tumorigenesis.
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4324-9
PMID: 15738393
-
Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer.
Clin Cancer Res. 2005 Mar 15;11(6):2285-92
PMID: 15788678
-
All-trans retinoic acid inhibits the cell proliferation but enhances the cell invasion through up-regulation of c-met in pancreatic cancer cells.
Cancer Lett. 2005 Jun 28;224(2):303-10
PMID: 15914280
-
The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target.
Clin Cancer Res. 2005 Nov 1;11(21):7785-93
PMID: 16278400
-
Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer.
Int J Cancer. 2006 Jan 15;118(2):405-11
PMID: 16052519
-
Important clues to the diagnosis of pancreatic cancer.
Rocz Akad Med Bialymst. 2005;50:69-72
PMID: 16358942
-
C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells.
Scand J Gastroenterol. 2000 Jan;35(1):90-5
PMID: 10672841
-
Evaluation of DNA fragment sizing and quantification by the agilent 2100 bioanalyzer.
Clin Chem. 2000 Nov;46(11):1851-3
PMID: 11067828
-
Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis.
Eur J Clin Invest. 2001 Oct;31(10):865-75
PMID: 11737224
-
Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma.
Cancer Res. 2002 Jan 15;62(2):589-96
PMID: 11809714
-
Inflammation and the development of pancreatic cancer.
Surg Oncol. 2002 May;10(4):153-69
PMID: 12020670
-
Met, metastasis, motility and more.
Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
PMID: 14685170
-
Pancreatic Cancer Registry in Japan: 20 years of experience.
Pancreas. 2004 Apr;28(3):219-30
PMID: 15084961
-
Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions.
Cancer Res. 2004 May 1;64(9):3215-22
PMID: 15126362