THE RELATIONSHIP BETWEEN EXPRESSION OF SMAD AND PROLIFERATION ENHANCEMENT THROUGH TGF-β SIGNALING PATHWAY IN PANCREATIC CANCER CELLS

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Background and Aims: To investigate the role of transcription factor Smad in tumor cell activation, we examined changes in the expression of Smads mRNA in transforming growth factor-β (TGF-β) stimulated tumor cells. Methods: Pancreatic cancer cell proliferation was monitored using the 3-(4, 5-dimethlthiazol-2-yl)-2, 5-diphenyltetrazolium bromide dye reduction method (MTT assay). Furthermore, Smad expression and TGF-β-mediated changes in the Smads of four human pancreatic cancer cell lines (BxPC-3, Capan-2, MIA PaCa-2, and SW 1990) were investigated using the quantitative real-time reverse transcription-polymerase chain reaction. Results: TGF-β enhanced the proliferation of human pancreatic cancer cells. The expression of Smad 2 and 3 (but not Smad 4) mRNAs was decreased after TGF-P stimulation in BxPC-3, Capan-2, and MIA PaCa-2 cells. In MIA PaCa-2 cells, Smad 4 mRNA expression was significantly increased. The attenuation of Smad 7 mRNA expression was common to these three cell lines. The expression of Smad 2 and Smad 4 mRNAs was significantly decreased in SW 1990 cells. However, the expression of Smad 6 and Smad 7 mRNAs did not significantly change in this cell line. Conclusions: Our results suggest that TGF-β acts as both the promoter and the suppressor for pancreatic cancer cells via alteration of Smads expression, and participates in the regulation of tumor proliferation.
名古屋市立大学の論文
2004-06-28