| Literature DB >> 15110786 |
Takaaki Imamura1, Fumihiko Kanai, Takayuki Kawakami, Jazag Amarsanaa, Hideaki Ijichi, Yujin Hoshida, Yasuo Tanaka, Tsuneo Ikenoue, Keisuke Tateishi, Takao Kawabe, Yoshihiro Arakawa, Makoto Miyagishi, Kazunari Taira, Osamu Yokosuka, Masao Omata.
Abstract
Smad4 is a tumor-suppressor gene that is lost or mutated in 50% of pancreatic carcinomas. Smad4 is also an intracellular transmitter of transforming growth factor-beta (TGF-beta) signals. Although its tumor-suppressor function is presumed to reside in its capacity to mediate TGF-beta-induced growth inhibition, there seems to be a Smad4-independent TGF-beta signaling pathway. Here, we succeeded in establishing Smad4 knockdown (S4KD) pancreatic cancer cell lines using stable RNA interference. Smad4 protein expression and TGF-beta-Smad4 signaling were impaired in S4KD cells, and we compared the proteomic changes with TGF-beta stimulation using two-dimensional gel electrophoresis (2-DE) and mass spectrometry. We identified five proteins that were up-regulated and seven proteins that were down-regulated; 10 of them were novel targets for TGF-beta. These proteins function in processes such as cytoskeletal regulation, cell cycle, and oxidative stress. Introducing siRNA-mediated gene silencing into proteomics revealed a novel TGF-beta signal pathway that did not involve Smad4.Entities:
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Year: 2004 PMID： 15110786 DOI： 10.1016/j.bbrc.2004.04.029
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575