Abstract
Id proteins, also known as inhibitors of DNA binding or inhibitors of differentiation, are upregulated in a variety of neoplasms, especially in conjunction with high-grade, poorly differentiated tumours, whereas differentiated tissues have little to no Id expression. The helix-loop-helix (HLH) family of transcription factors, which the four Id genes are part of, controls transcription by binding to and sequestering HLH complexes. By doing immunohistochemistry utilising a medulloblastoma tissue microarray with 44 distinct medulloblastomas and 10 normal control cerebella, and testing antibodies specific for Id1, Id2, Id3, and Id4 it was hypothesised that Id proteins are overexpressed in medulloblastomas.
A semi-quantitative staining score that considered staining intensity and the percentage of immunoreactive cells was implemented. Id1 was not found in medulloblastoma or normal cerebella, but it was strongly expressed in the endothelial nuclei of tumour arteries in 77% of tumours. In medulloblastoma, Id2 expression was more prominent than in normal cerebella (median staining score: 3). Id3 expression was seen in some neurons of the growing cerebellar cortex, but it was dramatically upregulated in tumour endothelial cells and medulloblastoma (median labelling score: 11).
Id4 was not expressed in either tumour cells or normal cerebella. By modifying the expression of essential cell cycle regulatory proteins in favour of cell proliferation, Id2 or Id3 overexpression induced proliferation in medulloblastoma cell lines. This research demonstrates that enhanced Id2 and Id3 expression in medulloblastoma may play a role in tumour cell proliferation and survival and that Id1 expression in endothelial cells may contribute to angiogenic processes.