TGF-beta1 signal pathway may contribute to rhabdomyosarcoma development by inhibiting differentiation.
Overexpression of transforming growth factor-beta1 (TGF-beta1) and its downstream molecules in the rhabdomyosarcoma (RMS) RD cell line has been reported previously, but the regulatory role of TGF-beta1 on RMS has not been studied extensively. In the present study, we showed that expression of TGF-beta1 and its downstream molecules type II TGF-beta receptor (TbetaRII) and Smad4 was significantly higher in RMS than in normal skeletal muscle, and there was a significant relationship between TGF-beta1 expression and histological grade. Gene silencing with TGF-beta1 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-beta1-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-beta1 shRNA increased staining for myosin. These results provide new insight into the biological function of TGF-beta1 in malignant tumors, and imply that the TGF-beta1 signal pathway is a potential therapeutic target for drugs that induce differentiation of RMS.
Wang
Shouli
S
Department of Pathology, Soochow University School of Medicine, Suzhou, China. wangsoly112@hotmail.com
Guo
Lingchuan
L
Dong
Liang
L
Guo
Lingling
L
Li
Shigang
S
Zhang
Jiajia
J
Sun
Maomin
M
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D034622:RNA Interference; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D012208:Rhabdomyosarcoma / Q000209:etiology* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II