Nuclear SMAD2 Restrains Proliferation of Glioblastoma

作者：Yu, Yunhu; Ran, Qishan^*

来源：Cellular Physiology and Biochemistry, 2015, 35(5): 1756-1763.

DOI：10.1159/000373987

• Glioblastoma multiforme (GBM)
• Transforming growth factor beta (TGF beta)
• SMAD2
• SMAD3
• p21
• Cancer cell growth

Aims: Although TGF beta receptor signaling has been shown to play a role in regulation of the growth and metastasis of glioblastoma multiforme (GBM), the downstream pathway through either SMAD2 or SMAD3 has not been elucidated. In this study, we investigate whether nuclear SMAD2 can restrain the proliferation of glioblastoma. Methods: A total of 23 resected specimens from GBM patients were collected for SMAD2 detection. Human GBM cell line A172, U87mg, D341m and Hs683 were maintained in Dulbecco's modified Eagle's medium and transfected with SMAD2 and SMAD3 shRNA plasmids. Gene expression was detected by RT-qPCR and Western and cell growth were detected by MTT assay. Results: Our results showed that the phosphorylated SMAD2 (pSMAD2, the nuclear and functional form of SMAD2) levels in GBM were significantly lower than the paired normal brain tissue in patients. Depletion of SMAD2, but not SMAD3, significantly abolished the inhibitory effects of TGF beta 1 on the growth of GBM cells, possibly through pSMAD2-mediated increases in cell-cycle inhibitor, p27. Conclusion: Our data suggest that TGF beta/SMAD2 signaling cascades restrains growth of GBM.

• 出版日期2015
• 单位遵义医科大学