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Differentiation-inducing factor-1 (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway

Oncogene volume 22, pages 548–554 (2003)Cite this article

Abstract

Differentiation-inducing factor-1 (DIF-1) is a chlorinated hexaphenone isolated from Dictyostelium. DIF-1 exhibits antitumor activity in several types of mammalian tumor cells, although the underlying mechanisms remain unknown. On the other hand, recent studies indicate that constitutively activated STAT3 acts as an oncogene and could be a target for antitumor drug. In the present study, we examined the effects of DIF-1 on proliferation of gastric cancer cell lines as well as on its signal transduction pathways, focusing mainly on STAT proteins. DIF-1 inhibited proliferation of gastric cancer cells. Western blot analysis and electrophoretic mobility shift assay showed that DIF-1 inhibited STAT3 activity in an MEK-ERK-dependent manner in gastric cancer cell lines, AGS and MKN28. Moreover, blockade of STAT3 activity by ectopic expression of dominant-negative STAT3 or the Janus kinase inhibitor, tyrphostin AG490, inhibited cell growth of AGS cells. These results suggest that STAT3 activity plays an important role for cell growth in AGS cells, and raises the possibility that inhibition of STAT3 activity is one of the mechanisms responsible for the antitumor effect of DIF-1 in these cells.

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Acknowledgements

We thank Dr Eri Iwai-Kanai for her valuable support. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Culture and Science of Japan (11370130, 11877090, and 11670496) and a Grant-in-Aid for Research for the Future Program from the Japanese Society for the Promotion of Science (No. JSPS-RFTF97100201).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Kanai, Yoshitaka Konda, Toshio Nakajima, Yoshio Izumi, Naoki Kanda, Apichart Nanakin & Tsutomu Chiba

  2. Department of Molecular Physiology, Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi 3-39-15, 371-8512, Maebashi, Japan

    Yuzuru Kubohara

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  1. Masashi Kanai
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Correspondence to Yoshitaka Konda.

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Kanai, M., Konda, Y., Nakajima, T. et al. Differentiation-inducing factor-1 (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway. Oncogene 22, 548–554 (2003). https://doi.org/10.1038/sj.onc.1206109

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