Expression analysis of PMP22/Gas3 in premalignant and malignant pancreatic lesions.
PMP22 is a structural protein of Schwann cells, but it also influences cell proliferation. In the present study, quantitative RT-PCR (QRT-PCR) and immunohistochemistry were used to determine PMP22 mRNA levels and to localize PMP22 in the normal pancreas (n=20), chronic pancreatitis (CP) (n=22), pancreatic ductal adenocarcinoma (PDAC) (n=31), intraductal papillary mucinous neoplasms (IPMN) (n=9), mucinous cystic tumors (MCN) (n=4), and in a panel of PanIN lesions (n=29). PMP22 mRNA levels were significantly higher in CP (3-fold) and PDAC (2.5-fold), compared to normal pancreatic tissues. PMP22 expression was restricted to nerves in the normal pancreas, while in CP and PDAC PMP22 was also expressed in PanIN lesions and in a small percentage of pancreatic cancer cells. PMP22 was weak to absent in the tumor cells of IPMNs and MCNs. PMP22 mRNA was present at different levels in cultured pancreatic cancer cells and up-regulated by transforming growth factor (TGF)-beta1 in 2 of 8 of these cell lines. In conclusion, PMP22 expression is present in both CP and PDAC tissues. Its expression in PanIN lesions and some pancreatic cancer cells in vitro and in vivo suggests a role of PMP22 in the neoplastic transformation process from the normal pancreas to pre-malignant lesions to pancreatic cancer.
Li
Junsheng
J
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Kleeff
Jörg
J
Esposito
Irene
I
Kayed
Hany
H
Felix
Klaus
K
Giese
Thomas
T
Büchler
Markus W
MW
Friess
Helmut
H
D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009185:Myelin Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009185:Myelin Proteins; C073687:PMP22 protein, human