Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K-Akt pathway activation in glioblastoma and prostate cancer
Mehrian-Shai, R; Chen, CD; Shi, T; Horvath, S; Nelson, SF; Reichardt, JKV; Sawyers, CL
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2007
卷号104期号:13页码:5563-5568
关键词brain cancer microarray
通讯作者Mehrian-Shai, R (reprint author), Univ So Calif, Inst Genet Med, CSC, IGM 263, 2250 Alcazer St, Los Angeles, CA 90033 USA.,mehrian@usc.edu ; cdchen@sibs.ac.cn
英文摘要PTEN is an important tumor-suppressor gene associated with many cancers. Through expression profiling of glioblastoma tissue samples and prostate cancer xenografts, we identified a molecular signature for loss of the PTEN tumor suppressor in glioblastoma and prostate tumors. The PTEN signature consists of a minimum of nine genes, several of which are involved in various pathways already implicated in tumor formation. Among these signature genes, the most significant was an increase in insulin growth factor-binding protein 2 (IGFBP-2) mRNA. Up-regulation of IGFBP-2 was confirmed at the protein level by Western blot analysis and validated in samples not included in the microarray analysis. The link between IGFBP-2 and PTEN was of particular interest because elevated serum IGFBP-2 levels have been reported in patients with prostate and brain tumors. To further investigate this link, we determined that IGFBP-2 expression is negatively regulated by PTEN and positively regulated by phosphaticlylinositol 3-kinase (PI3K) and Akt activation. In addition, Akt-driven transformation is impaired in IGFBP2(-/-) mouse embryo fibroblasts, implicating a functional role for IGFBP-2 in PTEN signaling. Collectively, these studies establish that PTEN and IGFBP-2 expression are inversely correlated in human brain and prostate cancers and implicate serum IGFBP-2 levels as a potential serum biomarker of PTEN status and PI3K Akt pathway activation in cancer patients.
学科主题Science & Technology - Other Topics
类目[WOS]Multidisciplinary Sciences
关键词[WOS]TUMOR-SUPPRESSOR GENE ; FACTOR BINDING-PROTEIN-2 ; EXPRESSION ; IDENTIFICATION ; CELLS ; MICE ; PROGRESSION ; PTEN/MMAC1 ; PREDICTION ; GLIOMAS
收录类别SCI
语种英语
WOS记录号WOS:000245331700056
内容类型期刊论文
版本出版稿
源URL[http://202.127.25.143/handle/331003/1623]  
专题上海生化细胞研究所_上海生科院生化细胞研究所
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Mehrian-Shai, R,Chen, CD,Shi, T,et al. Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K-Akt pathway activation in glioblastoma and prostate cancer[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2007,104(13):5563-5568.
APA Mehrian-Shai, R.,Chen, CD.,Shi, T.,Horvath, S.,Nelson, SF.,...&Sawyers, CL.(2007).Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K-Akt pathway activation in glioblastoma and prostate cancer.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,104(13),5563-5568.
MLA Mehrian-Shai, R,et al."Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K-Akt pathway activation in glioblastoma and prostate cancer".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104.13(2007):5563-5568.
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