Overexpression of transforming growth factor‐β1 (TGF‐β1) and its downstream molecules in the rhabdomyosarcoma (RMS) RD cell line has been reported previously, but the regulatory role of TGF‐β1 on RMS has not been studied extensively. In the present study, we showed that expression of TGF‐β1 and its downstream molecules type II TGF‐β receptor (TβRII) and Smad4 was significantly higher in RMS than in normal skeletal muscle, and there was a significant relationship between TGF‐β1 expression and histological grade. Gene silencing with TGF‐β1 short‐hairpin RNA (shRNA)‐expressing vectors significantly decreased the growth of RD cells, which was confirmed by caspase‐3 (in vitro) and TUNEL (in vivo) assays. Moreover, a proportion of treated rhabdomyosarcoma (RD) cells changed to a round shape from the normal fusiform or polygonal shape and expressed myofilaments. Myogenin is one of the myogenic differentiation genes (MyoD) family of myogenic regulators, and was obviously higher in TGF‐β1‐shRNA‐treated tumors than it in control at the mRNA and protein level. Immunohistochemical staining with myogenic differentiation markers such as myosin and desmin in subcutaneous RMS tissue showed that TGF‐β1 shRNA increased staining for myosin. These results provide new insight into the biological function of TGF‐β1 in malignant tumors, and imply that the TGF‐β1 signal pathway is a potential therapeutic target for drugs that induce differentiation of RMS.
(Cancer Sci 2010; 101: 1108–1116)