TGF-β regulates invasive behavior of human pancreatic cancer cells by controlling Smad expression
Journal Title: Archives of Medical Science - Year 2007, Vol 3, Issue 3
Abstract
Introduction: To investigate the role of Smads in tumor cell activation, we examined changes in Smad expression as well as changes in proliferative and invasive behaviors in transforming growth factor-β (TGF-β) – stimulated pancreatic cancer cells. Material and methods: Expression of TGF-β receptor type I (TβR-I) and type II (TβR-II) was determined using RT-PCR and Western blot analysis in the human pancreatic cancer cell lines BxPC-3, Capan-2, and PANC-1. TGF-β-mediated changes in Smad mRNA expression were examined using quantitative real-time RT-PCR. Proliferation of pancreatic cancer cells was monitored using an MTT assay and cell counting. Invasive behavior was examined using a Matrigel double-chamber assay. Results: TβR-I and TβR-II were expressed in all three cell lines studied here at the mRNA and protein level. Smad2/3 mRNA expression was decreased after TGF-β stimulation in all three cell lines, while Smad4 mRNA expression remained unchanged. Smad6/7 mRNA expression was also attenuated in all three cell lines. TGF-β enhanced the invasive capacity of all three cell lines, but had no effect on the proliferative behavior. Anti-TβR-II antibody inhibited this TGF-β-enhanced invasive potential in pancreatic cancer cells. Conclusions: The Smad pathway, particularly down-regulation of Smad2/3 and Smad6/7, may be responsible for TGF-β-induced invasion of human pancreatic cancer cells.
Authors and Affiliations
Hirozumi Sawai, Akira Yasuda, Nobuo Ochi, Hiroki Takahashi, Takehiro Wakasugi, Masaaki Azuma, Yoichi Matsuo, Hitoshi Funahashi, Mikinori Sato, Yoshimi Akamo, Hiromitsu Takeyama, Tadao Manabe
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