Inhibition of TGF-ß1 on Gli2 expression was promoted by TNF-α in primary leukemia cells.

ABSTRACT

PURPOSE: Hedgehog (Hh) signaling pathway regulates a variety of tumors-related diseases including leukemia. Whether inhibition of TGF-ß1 on Gli2 expression is promoted by TNF-α in primary leukemia cells remains to be determined. METHODS: Primary leukemia cells were treated with TGF-ß1, TNF-α or SIS3 at different concentrations. Gli2 expression was detected by quantitative real-time PCR and western blot analyses. RESULTS: We found that TGF-ß significantly decreased Gli2 expression, and co-treatment with TNF-αfurther decreased Gli2 expression in primary leukemia cells. TNF-α can increased TGF-ßRI and TGF-ßRII protein expression in primary leukemia cells, while SIS3 inhibited the effect of TGF-ß. CONCLUSION: Our results suggest that Gli2 expression in primary leukemia cells is induced by TGF-ß in a Smad3-dependent manner, and independent of Hh receptor signaling.