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Transforming growthfactor-β1 signalingcontributes to Caco-2cell growthinhibition induced by1,25(OH)2D3 Anping ChenBernard H. DavisMichael D. Sitrin2002 год

Transforming growth factor-β1 signaling contributes to Caco-2 cell growth inhibition induced by 1,25(OH)2D3
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Аннотация: Growth of Caco-2 and many cancer cells is inhibited by 1,25(OH) 2 D 3 . Whereas TGF-β1 inhibits normal colonic epithelial cell growth, most human colon cancer-derived cells, including Caco-2 and SW480 cells, are resistant to it. The mechanisms underlying these antiproliferative actions and resistance to TGF-β growth inhibition are largely unknown. We observed that 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] sensitized Caco-2 and SW480 cells to TGF-β1 growth inhibitory effects. Versus 1,25(OH) 2 D 3 alone, the combination of 1,25(OH) 2 D 3 and TGF-β1 significantly reduced cell numbers. Also, the amount of active TGF-β1 was increased (∼4-fold) by this secosteroid in conditioned media from Caco-2 cells. The 1,25(OH) 2 D 3 increased the expression of IGF-II receptors (IGF-IIR), which facilitated activation of latent TGF-β1, and was found to activate TGF-β signaling in Caco-2 cells. By using neutralizing antibodies to human TGF-β1, we showed that this cytokine contributes to secosteroid-induced inhibition of Caco-2 cell growth. Also, 1,25(OH) 2 D 3 was found to enhance the type I TGF-β receptor mRNA and protein abundance in Caco-2 cells. Whereas the 1,25(OH) 2 D 3 -induced sensitization of Caco-2 cells to TGF-β1 was IGF-IIR independent, the type I TGF-β1 receptor was required for this sensitization. Thus 1,25(OH) 2 D 3 treatment of Caco-2 cells results in activation of latent TGF-β1, facilitated by the enhanced expression of IGF-IIR by this secosteroid. Also, 1,25(OH) 2 D 3 sensitized Caco-2 cells to growth inhibitory effects of TGF-β1, contributing to the inhibition of Caco-2 cell growth by this secosteroid.
Год издания: 2002
Авторы: Anping Chen, Bernard H. Davis, Michael D. Sitrin, Thomas A. Brasitus, Marc Bissonnette
Издательство: American Physiological Society
Источник: AJP Gastrointestinal and Liver Physiology
Ключевые слова: TGF-β signaling in diseases, Growth Hormone and Insulin-like Growth Factors, Cancer, Hypoxia, and Metabolism
Другие ссылки: AJP Gastrointestinal and Liver Physiology (HTML)
PubMed (HTML)