Notch Signaling Enhances Nestin Expression in Gliomas<sup><a href="#FN1" rid="FN1" class=" fn">1</a>,</sup><sup><a href="#FN2" rid="FN2" class=" fn">*</a></sup>

Alan Shih

Eric Holland

^{Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA}

^{Department of Surgery (Neurosurgery), Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA}

Address all correspondence to: Eric C. Holland, 1275 York Avenue, New York, NY 10021. E-mail: gro.ccksm@ednalloh

Received 2006 Jul 28; Revised 2006 Sep 28; Accepted 2006 Oct 2.

Abstract

Recent findings suggest that Notch signaling is active in brain tumors and stem cells and that stem cells or cells with progenitor characteristics contribute to brain tumor formation. These stem cells are marked by expression of several markers including nestin, an intermediate filament protein. We have studied how the Notch signaling pathway affects nestin expression in brain tumors. We find that Notch receptors and ligands are expressed in vitro and in human samples of glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity activates the nestin promoter. Activation of the Notch pathway also occurs in a glioblastoma multiforme mouse model induced by Kras, with translational regulation playing a role in Notch expression. Combined activation of Notch and Kras in wild-type nestin-expressing cells leads to their expansion within the subventricular zone and retention of proliferation and nestin expression. However, activation of Notch alone is unable to induce this cellular expansion. These data suggest that Notch may have a contributing role in the stem-like character of glioma cells.

Keywords: Glioma, nestin, mouse model, Notch, stem cell

Abstract

Acknowledgements

We thank Hiroyuki Momota for critical suggestions on the manuscript; Edward Nerio and Jim Finney for technical assistance; Veronique Bourdon for microarray analysis; and David Anderson, Gerry Weinmaster, and Urban Lendahl for the reagents.

Acknowledgements

Footnotes

^{Laboratory work was supported by the Kleeberg Foundation, Kirby Foundation, and National Institutes of Health (NIH) grants UO1CA894314-1 and RO1 CA099489 to E.C.H. A.H.S. was supported by NIH MSTP grant GM07739.}

^{This article refers to supplementary material, which is designated by “W” (i.e.,}Table W1) and is available online at www.bcdecker.com.

Footnotes

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