Aberrant signaling of TGF-β1 by the mutant Smad4 in gastric cancer cells

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Title
Aberrant signaling of TGF-β1 by the mutant Smad4 in gastric cancer cells
Author(s)
Hyang Ran Ju; U Hee Jung; Chung Hee Sonn; Suk Ran Yoon; Jun Ho Jeon; Young Yang; Kee Nyung Lee; In Pyo Choi
Bibliographic Citation
Cancer Letters, vol. 196, no. 2, pp. 197-206
Publication Year
2003
Abstract
TGF-β1 has been known to suppress the growth of gastric cancer cells. Interestingly, TGF-β1 treatment increased the proliferation of human gastric cancer cell line, SNU-216 cells, while it reduced the proliferation of other tumor cells including SNU-620 cells. TGF-β1-mediated down-regulation of c-Myc and induction of p21CIP1 were observed in SNU-620, but there was no change in SNU-216 in response to TGF-β1. Similarly, TGF-β1 receptors were upregulated by TGF-β1 treatment in SNU-620, but they were not responded in SNU-216. By a single strand conformation polymorphism analysis, a repeated insertion of 37 nucleotides in the exon 8 of Smad4, resulting in premature termination at codon 362, was found in SNU-216. Furthermore, this truncated Smad4 functioned as a dominant negative form in TGF-β1-mediated reporter activity and TGF-β1 receptor expression. However, the proliferation of tumor cells was not affected by Smad4 mutation, but it was modulated by PD98059. Taken together, a mutation in Smad4 in addition to mitogen-activated protein kinase altered the TGF-β1-mediated signaling, which is one of key events of gastric tumorigenesis.
Keyword
Gastric tumorMitogen-activated protein kinaseMutationSmad4TGF-β1
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0304-3835(03)00237-4
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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