High TGFβ-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene
High TGFβ-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene
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DOI：
10.1016/j.ccr.2006.11.023
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发表时间：
2007-02-01
期刊：
影响因子：
50.3
通讯作者：
Seoane, Joan
中科院分区：
文献类型：
--
作者：
Bruna, Alejandra;Darken, Rachel S.;Seoane, Joan
转化生长因子β在正常上皮细胞和早期肿瘤中发挥肿瘤抑制作用，并在晚期肿瘤中成为致癌因子。转化生长因子β恶性作用的分子机制尚未完全阐明。我们证明高的转化生长因子β-Smad活性存在于侵袭性的、高增殖性的胶质瘤中，并且在胶质瘤患者中预后不良。通过分析原代培养的患者来源的胶质瘤和人脑胶质瘤活检组织，我们通过转录转录方法和分析原代培养的患者来源的胶质瘤和人脑胶质瘤活检组织，识别了转化生长因子β致癌反应的机制和分子决定因素。在含有未甲基化PDGF-B基因的胶质瘤中，转化生长因子β-Smad途径通过诱导PDGF-B促进增殖。PDGF-B基因的表观遗传调控决定了转化生长因子β是否作为致癌因子在人脑胶质瘤中诱导PDGF-B和增殖。
TGF beta acts as a tumor suppressor in normal epithelial cells and early-stage tumors and becomes an oncogenic factor in advanced tumors. The molecular mechanisms involved in the malignant function of TGF beta are not fully elucidated. We demonstrate that high TGF beta-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma. We discern the mechanisms and molecular determinants of the TGF beta oncogenic response with a transcriptomic approach and by analyzing primary cultured patient-derived gliomas and human glioma biopsies. The TGF beta-Smad pathway promotes proliferation through the induction of PDGF-B in gliomas with an unmethylated PDGF-B gene. The epigenetic regulation of the PDGF-B gene dictates whether TGF beta acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma.