TY - JOUR
T1 - TWIST is expressed in human gliomas and promotes invasion
AU - Elias, Maria C.
AU - Tozer, Kathleen R.
AU - Silber, John R.
AU - Mikheeva, Svetlana
AU - Deng, Mei
AU - Morrison, Richard S.
AU - Manning, Thomas C.
AU - Silbergeld, Daniel L.
AU - Glackin, Carlotta A.
AU - Reh, Thomas A.
AU - Rostomily, Robert C.
N1 - Funding Information:
Abbreviations: bHLH, basic helix–loop–helix; CNS, central nervous system; FBS, fetal bovine serum; GBM, glioblastoma; GS, gliosarcoma; H&E, hematoxylin and eosin; HGF, hepatocyte growth factor; IGF, insulin-like growth factor Address all correspondence to: Robert C. Rostomily, MD, Department of Neurological Surgery, Box 356470, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-6470. E-mail: rosto@u.washington.edu 1This work was supported by National Institutes of Health grants KO8 NS02217 (R.C.R.), NS42123 (R.S.M.), CA82622 (J.R.S.), NS28308 (T.A.R.), and T32-NS00714424 (UW Department of Neurological Surgery). Additional support was provided by grants from The Seattle Foundation (R.C.R.) and University of Washington HHMI Pilot Study (R.C.R.). 2Maria C. Elias and Kathleeen R. Tozer contributed equally to the manuscript. Received 27 May 2004; Revised 21 April 2005; Accepted 18 May 2005.
PY - 2005/9
Y1 - 2005/9
N2 - TWIST is a basic helix-loop-helix (bHLH) transcription factor that regulates mesodermal development, promotes tumor cell metastasis, and, in response to cytotoxic stress, enhances cell survival. Our screen for bHLH gene expression in rat C6 glioma revealed TWIST. To delineate a possible oncogenic role for TWIST in the human central nervous system (CNS), we analyzed TWIST message and protein expression in gliomas and normal brain. TWIST was detected in the large majority of human glioma-derived cell lines and human gliomas examined. Increased TWIST mRNA levels were associated with the highest grade gliomas, and increased TWIST expression accompanied transition from low grade to high grade in vivo, suggesting a role for TWIST in promoting malignant progression. In accord, elevated TWIST mRNA abundance preceded the spontaneous malignant transformation of cultured mouse astrocytes hemizygous for p53. Overexpression of TWIST protein in a human glioma cell line significantly enhanced tumor cell invasion, a hallmark of high-grade gliomas. These findings support roles for TWIST both in early glial tumorigenesis and subsequent malignant progression. TWIST was also expressed in embryonic and fetal human brain, and in neurons, but not glia, of mature brain, indicating that, in gliomas, TWIST may promote the functions also critical for CNS development or normal neuronal physiology.
AB - TWIST is a basic helix-loop-helix (bHLH) transcription factor that regulates mesodermal development, promotes tumor cell metastasis, and, in response to cytotoxic stress, enhances cell survival. Our screen for bHLH gene expression in rat C6 glioma revealed TWIST. To delineate a possible oncogenic role for TWIST in the human central nervous system (CNS), we analyzed TWIST message and protein expression in gliomas and normal brain. TWIST was detected in the large majority of human glioma-derived cell lines and human gliomas examined. Increased TWIST mRNA levels were associated with the highest grade gliomas, and increased TWIST expression accompanied transition from low grade to high grade in vivo, suggesting a role for TWIST in promoting malignant progression. In accord, elevated TWIST mRNA abundance preceded the spontaneous malignant transformation of cultured mouse astrocytes hemizygous for p53. Overexpression of TWIST protein in a human glioma cell line significantly enhanced tumor cell invasion, a hallmark of high-grade gliomas. These findings support roles for TWIST both in early glial tumorigenesis and subsequent malignant progression. TWIST was also expressed in embryonic and fetal human brain, and in neurons, but not glia, of mature brain, indicating that, in gliomas, TWIST may promote the functions also critical for CNS development or normal neuronal physiology.
KW - Brain tumor
KW - Cancer
KW - Invasion
KW - Neuron
KW - Oncogene
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U2 - 10.1593/neo.04352
DO - 10.1593/neo.04352
M3 - Article
C2 - 16229805
AN - SCOPUS:33644873765
VL - 7
SP - 824
EP - 837
JO - Neoplasia (United States)
JF - Neoplasia (United States)
SN - 1522-8002
IS - 9
ER -