生物谷报道：美国研究人员新确认了一种基因与脑瘤发病有关，将来有望开发出以这种基因为靶向的新型抗癌药物。
得克萨斯大学安德森癌症中心的研究人员在新一期美国《国家科学院学报》（PNAS）上报告说，对老鼠进行的实验表明，一种名为“胰岛素样生长因子结合蛋白2（IGFBP2）”的基因如果过度表达，会导致其脑部形成星状细胞瘤和寡树突胶质细胞瘤。这两种恶性肿瘤属于最常见的神经胶质瘤。
此前的研究显示，IGFBP2基因与多种类型的癌症有联系。但一般来说，一种基因与某种癌症有关，并不代表它就是致癌基因。而安德森癌症中心的研究人员以老鼠为研究对象，利用一种“基因转移导入技术”进行多项对比实验，首次证实了IGFBP2基因是导致脑部肿瘤生成并恶化的直接原因之一。
神经胶质瘤是发生在神经胶质细胞中的肿瘤，对化疗的抵抗力极强。近几十年来，晚期神经胶质瘤患者的存活期几乎没有实质性延长。研究人员希望下一步能以IGFBP2基因为靶向，研制出新型药物，造福神经胶质瘤患者。（新华网）
原始出处:
Published online before print July 2, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0703145104
Insulin-like growth factor binding protein 2 promotes glioma development and progression
( glial-specific transgenic mouse model | oligodendroglioma )
Sarah M. Dunlap *, Joseph Celestino *, Hua Wang *, Rongcai Jiang *, Eric C. Holland ¶, Gregory N. Fuller *||, and Wei Zhang *||
*Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and ¶Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Edited by Webster K. Cavenee, University of California at San Diego School of Medicine, La Jolla, CA, and approved May 29, 2007 (received for review April 4, 2007)
Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression in many types of human cancer. In this study we used a glial-specific transgenic mouse model to examine the active role of IGFBP2 in tumorigenesis and progression. Our studies show that IGFBP2 coexpression results in progression to a higher-grade glioma in platelet-derived growth factor (PDGFB)-driven tumors. These anaplastic oligodendrogliomas are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. Combined expression of IGFBP2 or Akt with K-Ras was required to form astrocytomas, indicating that activation of two separate pathways is necessary for gliomagenesis. In ex vivo experiments, blockade of Akt by an inhibitor led to decreased viability of cells coexpressing IGFBP2 versus PDGFB expression alone. Thus, this study provides definitive evidence that IGFBP2 plays a key role in activation of the Akt pathway and collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma.
