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Title 

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

Authors 

Hyang Ran JuU Hee JungChung Hee SonnSuk Ran YoonJun Ho JeonYoung YangKee Nyung LeeIn Pyo Choi

Publisher 

Elsevier

Issue Date 

2003

Citation 

Cancer Letters, vol. 196, no. 2, pp. 197-206

Keywords 

gastric tumormitogen-activated protein kinasemutationSmad4TGF-β1protein p21Smad4 proteintransforming growth factor beta1cancer cell culturecell proliferation

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.

ISSN 

0304-3835

Link 

http://dx.doi.org/10.1016/S0304-3835(03)00237-4

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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