Shuang Liu, Feng Yin, Jianning Zhang, Wenhong Fan and Ming Fan
Accepted Abstracts: J Cancer Sci Ther
In the present 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 cell lines compared to normal astrocytes. 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, colony formation analysis and immunofluorescence showed that BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression, whereas the expression level of Skp2 protein decreased during this growth arrest and differentiation process. The results were consistent with real-time RT-PCR data. Furthermore, overexpression of BMPR-IB also 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. Our results suggest that decreased expression of BMPR-IB in most human glioblastoma cells contributes to glioma tumorigenicity and that overexpression of BMPR-IB may induce growth arrest and differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and in vivo . BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.
Shuang Liu has studied molecular biology and molecular therapeutics of brain tumor and stem cells for 10+ years, during which time she has been in charge many research projects about glioma and cancer stem cells, including two Chinese National Science Foundation (No: 30873029 and No: 81172384). She authored more than 20 peer-reviewed reports. Dr. Shuang is a member of the Chinese Neuroscience Society, and has served on the editorial boards for Chinese Journal of Integrated Traditional and Western Medicine for about 10 years.