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sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival

Sphingosine-1-phosphate receptor type 1 regulates glioma cel...

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中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Yuya Yoshida Mitsutoshi Nakada Naotoshi sugimoto Tomoya Harada Yasuhiko Hayashi Daisuke Kita Naoyuki Uchiyama Yutaka Hayashi Akihiro Yachie Yoh Takuwa Jun-ichiro Hamada Department of Neurosurgery Graduate School of Medical ScienceKanazawa University Department of physiology Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan Department of pediatrics Graduate School of Medical ScienceKanazawa UniversityKanazawaJapan

sphingosine-1-phosphate（s1p） is a bioactive lipid that signals through a family of G protein-coupled receptors consisting of 5 members termed s1p1-5,and it regulates cellular proliferation,migration and *** investigated the expression and role of s1p receptors in *** glioma expressed s1p1,s1p2,s1p3,and s1p5 by quantitative real-time pCR *** of the s1p1 was significantly lower in glioblastoma than in the normal brain（p ＜ 0.01） and diffuse astrocytoma（p ＜ 0.05）.Immunoblotting showed that normal brain expressed more s1p1 protein than did *** showed that s1p1 was localized predominantly in the astrocytes in the normal brain,but no staining was observed in *** of s1p1 expression correlated with poor survival of patients with glioblastoma（p ＜ 0.05）.s1p1 small interfering RNA promoted cell proliferation in high-expressor glioma cell lines（T98G,G112）.Cell proliferation was promoted by the pertussis toxin,which deactivates Gi/o type of G proteins;the s1p1 is exclusively coupled to these *** expression of the s1p1 in low-expressor cell lines（U87,U251） resulted in decreased cell growth and led to suppressed tumor growth in transplanted gliomas in ***,we found a significant association between the s1p1 expression and early growth response-1,a transcriptional factor that exhibits tumor suppression in glioblastoma cells（p ＜ 0.05）.These data indicate that the downregulation of s1p1 expression enhances the malignancy of glioblastoma by increasing cell proliferation and correlates with the shorter survival of patients with glioblastoma.

关键词： glioblastoma s1p receptors s1p1 receptor proliferation survival

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