title: Expression pattern of id proteins in medulloblastoma.
abstract: Inhibitor of DNA binding or inhibitor of differentiation (Id) proteins are up regulated in a variety of neoplasms, particularly in association with high-grade, poorly differentiated tumors, while differentiated tissues show little or no Id expression. The four Id genes are members of the helix-loop-helix (HLH) family of transcription factors and act as negative regulators of transcription by binding to and sequestering HLH complexes. We tested the hypothesis that Id proteins are overexpressed in medulloblastoma by performing immunohistochemistry using a medulloblastoma tissue microarray with 45 unique medulloblastoma and 11 normal control cerebella, and antibodies specific for Id1, Id2, Id3, and Id4. A semi-quantitative staining score that took staining intensity and the proportion of immunoreactive cells into account was used. Id1 was not detected in normal cerebella or in medulloblastoma cells, but 78 % of tumors showed strong Id1 expression in endothelial nuclei of tumor vessels. Id2 expression was scant in normal cerebella and increased in medulloblastoma (median staining score: 4). Id3 expression was noted in some neurons of the developing cerebellar cortex, but it was markedly up regulated in medulloblastoma (median staining score: 12) and in tumor endothelial cells. Id4 was not expressed in normal cerebella or in tumor cells. Id2 or Id3 overexpression drove proliferation in medulloblastoma cell lines by altering the expression of critical cell cycle regulatory proteins in favor of cell proliferation. This study shows that Id1 expression in endothelial cells may contribute to angiogenic processes and that increased expression of Id2 and Id3 in medulloblastoma is potentially involved in tumor cell proliferation and survival.
authors: The Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
authors: Andrew D
authors: AD
authors: Snyder
authors: Ashley N
authors: AN
authors: Dulin-Smith
authors: Ronald H
authors: RH
authors: Houston
authors: Ashley N
authors: AN
authors: Durban
authors: Bethany J
authors: BJ
authors: Brisbin
authors: Tyler D
authors: TD
authors: Oostra
authors: Jordan T
authors: JT
authors: Marshall
authors: Basil M
authors: BM
authors: Kahwash
authors: Christopher R
authors: CR
authors: Pierson
mesh_terms: D000293:Adolescent; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis*; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism*; D009928:Organ Specificity; D018709:Statistics, Nonparametric
chemical_list: D051796:Inhibitor of Differentiation Proteins; D018844:Cyclin-Dependent Kinases
references: Nature. 2001 Feb 22;409(6823):1067-70
references: 11234019
references: Dev Dyn. 1997 Jan;208(1):92-106
references: 8989524
references: Nat Immunol. 2001 Feb;2(2):165-71
references: 11175815
references: Oncogene. 2001 Dec 20;20(58):8317-25
references: 11840324
references: Acta Neuropathol. 2012 Apr;123(4):465-72
references: 22134537
references: Dev Biol. 1993 Nov;160(1):186-95
references: 8224536
references: Genes Dev. 2005 Mar 15;19(6):744-55
references: 15769946
references: Dev Dyn. 1995 Jun;203(2):163-73
references: 7655079
references: EMBO J. 1992 Jul;11(7):2563-71
references: 1628620
references: Dev Biol. 1992 Nov;154(1):1-10
references: 1426618
references: Mol Cancer Res. 2009 Jan;7(1):33-40
references: 19147535
references: Nucleic Acids Res. 1996 Jul 15;24(14):2813-20
references: 8759016
references: Nat Rev Cancer. 2005 Aug;5(8):603-14
references: 16034366
references: Nature. 2000 Oct 5;407(6804):592-8
references: 11034201
references: J Cell Physiol. 2002 Jan;190(1):21-8
references: 11807807
references: Acta Neuropathol. 2007 Aug;114(2):97-109
references: 17618441
references: J Clin Oncol. 2001 Aug 1;19(15):3470-6
references: 11481352
references: Nature. 2006 Jul 27;442(7101):471-4
references: 16810178
references: Trends Mol Med. 2004 Aug;10(8):387-92
references: 15310459
references: Glia. 1998 Dec;24(4):372-81
references: 9814817
references: Mol Cell Biol. 1997 Oct;17(10):5888-96
references: 9315646
references: J Neurosci. 2000 Aug 1;20(15):5756-63
references: 10908616
references: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7331-6
references: 12777630
references: Mol Cell Biol. 1997 Dec;17(12):6815-21
references: 9372912
references: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13543-8
references: 14578451
references: J Neurosurg Pediatr. 2010 Jun;5(6):608-14
references: 20515335
references: Neurochem Res. 2003 Jan;28(1):45-52
references: 12587662
references: Nature. 1999 Oct 14;401(6754):670-7
references: 10537105
references: Genes Dev. 1994 Jun 1;8(11):1270-84
references: 7926730
references: Trends Cell Biol. 2003 Aug;13(8):410-8
references: 12888293
references: Glia. 2002 Jun;38(4):329-38
references: 12007145