Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1

Background: in our previous study,we detected decreased expression of phospho-smad1/5/8 and its upstream signaling molecule,bone morphogenetic protein receptor ib subunit (bmpr-ib),in certain glioblastoma tissues,unlike normal brain tissues. in order to clarify the functional roles and mechanism of bmpr-ib in the development of glioblastoma,we studied the effects of bmpr-ib overexpression on glioblastoma cell lines in vitro and in vivo. methods: we selected glioblastoma cell lines u251,u87,sf763,which have different expression of bmpr-ib to be the research subjects. colony formation analysis and facs were used to detect the effects of bmpr-ib on the growth and proliferation of glioblastoma cells in vivo. immunofluresence was used to detect the differentiation changes after bmpr-ib overexpression or knocking-down. then we used subcutaneous and intracranial tumor models to study the effect of bmpr-ib on the growth and differentiation of glioblastoma cells in vivo. the genetic alterations involved in this process were examined by real-time pcr and western blot analysis.ed. results and conclusion: forced bmpr-ib expression in malignant human glioma cells,which exhibit lower expression of bmpr-ib,induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in g1. additionally,bmpr-ib overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. furthermore,overexpression of bmpr-ib inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with bmpr-ib-overexpressing glioblastoma cells. conversely,inhibition of bmpr-ib caused sf763 malignant glioma cells,a line known to exhibit high bmpr-ib expression that does not form tumors when used for xenografts,to show increased growth and regain tumorigenicity in a nude mouse model system,ultimately shortening the survival of these mice. we also observed significant accumulation of p21 and p27kip1 proteins in response to bmpr-ib overexpression. our study suggests that overexpression of bmpr-ib may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of bmpr-ib in human glioblastoma cells contributes to glioma tumorigenicity. bmpr-ib could represent a new potential therapeutic target for malignant human gliomas. © 2012 liu et al.; licensee biomed central ltd.