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Titolo:
Analysis of the Max-binding protein MNT in human medulloblastomas
Autore:
Sommer, A; Waha, A; Tonn, J; Sorensen, N; Hurlin, PJ; Eisenman, RN; Luscher, B; Pietsch, T;
Indirizzi:
Med Hsch Hannover, Inst Mol Biol, D-30623 Hannover, Germany Med Hsch Hannover Hannover Germany D-30623 ol, D-30623 Hannover, Germany Univ Bonn, Inst Neuropathol Med Einrichtungen, D-5300 Bonn, Germany Univ Bonn Bonn Germany D-5300 ol Med Einrichtungen, D-5300 Bonn, Germany Univ Wurzburg, Abt Neurochirurg, Wurzburg, Germany Univ Wurzburg Wurzburg Germany urg, Abt Neurochirurg, Wurzburg, Germany Univ Wurzburg, Abt Padiat Neurochirurg, Wurzburg, Germany Univ Wurzburg Wurzburg Germany t Padiat Neurochirurg, Wurzburg, Germany Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA Fred Hutchinson Canc Res Ctr Seattle WA USA 98104 , Seattle, WA 98104 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 6, volume: 82, anno: 1999,
pagine: 810 - 816
SICI:
0020-7136(19990909)82:6<810:AOTMPM>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR GENE; PRIMITIVE NEUROECTODERMAL TUMORS; HISTONE DEACETYLASE ACTIVITY; BRAIN-TUMORS; TRANSCRIPTIONAL REPRESSION; MOLECULAR ANALYSIS; CELL-GROWTH; MYC; AMPLIFICATION; 17P13.3;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Luscher, B Med Hsch Hannover, Inst Mol Biol, D-30623 Hannover, Germany MedHsch Hannover Hannover Germany D-30623 Hannover, Germany
Citazione:
A. Sommer et al., "Analysis of the Max-binding protein MNT in human medulloblastomas", INT J CANC, 82(6), 1999, pp. 810-816

Abstract

Medulloblastomas (MBs) are the most frequent malignant brain tumors in children. The molecular pathogenesis of these tumors is still poorly understood. Microsatellite and restriction-fragment-length polymorphism studies haverevealed allelic loss of genetic material on the short arm of chromosome 17 in the region 17p13 in approximately 50% of MBs, suggesting the presence of a tumor-suppressor gene in this region. A candidate for this putative tumor-suppressor is the MNT gene, located at 17p13.3 and encoding a Max-interacting nuclear protein with transcriptional-repressor activity. In this study, we analyzed MNT mRNA and protein expression in 44 MB samples, including32 primary tumors, 3 recurrent tumors and 9 MB cell lines. Allelic loss at17p13.3 was found in 49% of informative cases. RT-PCR showed MNT mRNA expression in all cases analyzed. Endogenous Mnt protein with an apparent molecular weight of 72 to 74 kDa was detected in lysates from MB cell lines. Thepresence and functional integrity of Mnt in MBs were tested in electrophoretic mobility-shift assays. These experiments demonstrated that Mnt interacts with Max, and that this heterodimer binds DNA specifically, suggesting afunctional bHLHZip domain of MB-derived Mnt. In support, single-strand conformation-polymorphism (SSCP) analyses revealed no mutation in the bHLHZip region. Deletion of the Mnt Sin3 interaction domain was shown to convert Mnt from an inhibitor of myc/rasco-transformation into a molecule capable of cooperating with Ras in transformation. This region therefore was screened for mutation by SSCP: again, no alterations were found. These findings indicate that the MNT gene located at 17p13.3 is not likely to be involved in the molecular pathogenesis of MBs. (C) 1999 Wiley-Liss, Inc.

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Documento generato il 09/07/20 alle ore 14:18:47