Overexpression of Smad2 and colocalization with TGF-beta1 in human pancreatic cancer.
Smad2 belongs to a family of cytoplasmic molecules that are critical components in the transforming growth factor beta (TGF-beta) signaling pathway. Upon ligand binding, the type II TGF-beta receptor (TbetaRII) heterodimerizes with and activates TGF-beta receptor type I (TbetaRI). Activated TbetaRI phosphorylates Smad2, which then heterodimerizes with Smad4, translocates into the nucleus, and subsequently effects gene transcription. Previously we have shown that pancreatic cancers overexpress TGF-betas and TbetaRII. Here, we show by northern blot analysis that Smad2 mRNA levels are significantly increased in pancreatic cancer samples in comparison with normal pancreatic tissues. By immunohistochemistry, Smad2 is present in the cancer cells of 67% of the pancreatic cancer samples. Analysis of serial sections reveals coexpression of Smad2 and TGF-beta1 in the cancer cells. Furthermore, TGF-beta1 increases steady-state levels of Smad2 mRNA in the TGF-beta1-sensitive pancreatic cancer cell line COLO-357. It is suggested that pancreatic cancer cells have the capacity to up-regulate Smad2 expression, which may lead to excessive activation of specific components of the TGF-beta-signaling pathway.
Kleeff
J
J
Department of Medicine, University of California, Irvine 92697, USA.
Friess
H
H
Simon
P
P
Susmallian
S
S
Büchler
P
P
Zimmermann
A
A
Büchler
M W
MW
Korc
M
M
D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012016:Reference Values; D051899:Smad2 Protein; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta