生物谷報道：美國研究人員新確認(rèn)了一種基因與腦瘤發(fā)病有關(guān)，將來有望開發(fā)出以這種基因為靶向的新型抗癌藥物。
得克薩斯大學(xué)安德森癌癥中心的研究人員在新一期美國《國家科學(xué)院學(xué)報》（PNAS）上報告說,，對老鼠進行的實驗表明,，一種名為“胰島素樣生長因子結(jié)合蛋白2（IGFBP2）”的基因如果過度表達(dá),，會導(dǎo)致其腦部形成星狀細(xì)胞瘤和寡樹突膠質(zhì)細(xì)胞瘤,。這兩種惡性腫瘤屬于最常見的神經(jīng)膠質(zhì)瘤。
此前的研究顯示,，IGFBP2基因與多種類型的癌癥有聯(lián)系,。但一般來說，一種基因與某種癌癥有關(guān),，并不代表它就是致癌基因,。而安德森癌癥中心的研究人員以老鼠為研究對象，利用一種“基因轉(zhuǎn)移導(dǎo)入技術(shù)”進行多項對比實驗,，首次證實了IGFBP2基因是導(dǎo)致腦部腫瘤生成并惡化的直接原因之一,。
神經(jīng)膠質(zhì)瘤是發(fā)生在神經(jīng)膠質(zhì)細(xì)胞中的腫瘤,，對化療的抵抗力極強。近幾十年來,，晚期神經(jīng)膠質(zhì)瘤患者的存活期幾乎沒有實質(zhì)性延長,。研究人員希望下一步能以IGFBP2基因為靶向，研制出新型藥物,，造福神經(jīng)膠質(zhì)瘤患者,。（新華網(wǎng)）
原始出處:
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.
