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Background Transforming growth factor beta(TGF-beta)plays an essential role in the regulation of normal physiologicprocesses of cells.TGF-beta has been shown to regulate several mitogen-activated protein kinases(MAPK)pathways inseveral epithelial cells.However,the effects of TGF-beta on soft tissue sarcoma are seldom reported.Our previousstudies suggested that there should be some other signal transduction pathways besides Smads,which are important toregulate the growth of human embryonal rhabdomyosarcoma(RMS)cells.In the present study,we examined theexpression and functional relations of extracellular signal-regulated kinase 2(ERK2)and Smad4 in human RMS tissueand a RMS cell line,RD.Methods RD cells and normal human primary skeletal myoblasts(Mb)were treated with TGF-beta1 to establish theexpression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence.Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMSand 23 specimens of normal skeletal muscles.Follow-up of specimens was performed 6 months to 70 months later.Results RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control,either the protein level or the mRNA level.And,exogenous TGF-beta1 stimulation can lead to higher expression of ERK2and its nuclear translocation,so TGF-beta1 can also activated MAPK(ERK2)pathway,resulting in a sustained activationof ERK2 for at least 2 hours.Immunohistochemistry analysis,however,showed that there was no correlation betweenERK2 and Smad4 protein.The overexpression of ERK2.and Smad4 had no indicative effects on histological subtypes,histological grading,gender,age,and prognosis.Conclusions In RMS,signaling of TGF-beta1 from cell surface to nucleus can also be directed through the MAPK(ERK2)pathway besides the TGF-beta1/Smads pathway.The activation of ERK2 by TGF-beta1 may be Smad4independent.Moreover,there may be some other tanglesome relationships between the TGF-betal/Smads pathway andthe MAPK pathway which takes part in the development,invasion and metastasis of tumor cells.
Background Transforming growth factor beta (TGF-beta) plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases (MAPK) pathways in ventral epithelial cells. However, the effects of Our previous study suggested that there should be some other signal transduction pathways besides Smads, which are important to regulate the growth of human embryonal rhabdomyosarcoma (RMS) cells. In the present study, we examined the expression and functional relations of extracellular signal-regulated kinase 2 (ERK2) and Smad4 in human RMS tissue and a RMS cell line, RD. Methods RD cells and normal human primary skeletal myoblasts (Mb) were treated with TGF-beta1 to establish the expression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMS and 23 specimens of normal skeletal muscles. Focus-up of specimens was performed for 6 months to 70 months later. Results RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control, either the protein level or the mRNA level.And, exogenous TGF-beta1 stimulation can lead to higher expression of ERK2 and its nuclear translocation, so TGF-beta1 can also activate MAPK (ERK2) pathway, resulting in a sustained activation of ERK2 for at least 2 hours. Immunohistochemical analysis, however, showed that there was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2.and Smad4 had no indicative effects on histological subtypes, histological grading, gender, age, and prognosis. Conclusions In RMS, signaling of TGF-beta1 from cell surface to nucleus can also be directed through the MAPK (ERK2) pathway besides the TGF-beta1 / Smads pathway. The activation of ERK2 by TGF-beta1 may be Smad4 dependent. More over, there may be some other tanglesome relationships between the TGF-beta / Smad pathway and MAPK pathway which takes part in the development, invasion and metastasis of tumor cells.