Expression And Function Of BMPs/Smad1 Signal Pathway In Glioma

BMPs play an essential role in cell fate determination, and smads proteins play akey role in transforming BMPs signal transduction. Although extensively investigated inmany tumors, smad1-associated pathway has only received limited study in glioma.In this study, we have examined one glioblastoma cell line-U251 and tissuespeciments of 60 gliomas: 20 astrocytomas(AST), 20 anaplastic astrocytomas(AAST),and 20 gliomblastoma multiform gradeâ…£(GBM).. We found that phospho-smad1decreased in U251 cell line and most malignant glioma tissues, and smad1 decreased inU251 and GBM tissues by Western blotting analysis compared with normal braintissues. Using RT-PCR and Western blot we detected the lower expression of BMPR-IBon most glioma tissues as well as U251 cells. Transient transfection of BMPR-IB,smad1, or both activated smad1 and caused transient apoptosis and differentiation ofU251 cells, accompanied by a significant increase in the activity of BRE-luciferasereporter and the expression levels of phospho-smad1 and GFAP compared withtransfection of empty vector. Treatment with an inhibitor smad protein-smad6significantly inhibited these effects. We then studied the effects of BMP-2 on U251 cells,and found that BMP-2 treatment of U251 cells delayed cell growth and inducedglioblastoma cell differentiation. Of note, we found a significant up-regulation ofBMPR-IB and P-smad1 in response to BMP-2.Our results suggested that the lower expressions of BMPR-IB and smad1 blockedthe activation of BMPs/smad1 signaling pathway in gliomas, over-expression ofBMPR-IB and smad1 could induce apoptosis and differentiation of U251 cells throughtheir activation of smad1. Our results also suggest that BMP-2 could regulate the growthand differentiation of gliomblastoma by autocrine or paracrine mode. BMPs/smad1signal pathway might provide a new therapeutic strategy for gliomas.