%0 Journal Article
%T Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer
%A Erik Noetzel
%A Jščrgen Veeck
%A Dieter Niederacher
%A Oliver Galm
%A Felicitas Horn
%A Arndt Hartmann
%A Ruth Knščchel
%A Edgar Dahl
%J BMC Cancer
%D 2008
%I BioMed Central
%R 10.1186/1471-2407-8-154
%X ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters.Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level. Interestingly, ID4 promoter methylation was a factor for unfavourable recurrence-free survival (P=0.036) and increased risk for lymph node metastasis (P=0.030).ID4 is indeed a novel tumour suppressor gene in normal human breast tissue and is epigenetically silenced during cancer development, indicating increased risk for tumour relapse. Thus, ID4 methylation status could serve as a prognostic biomarker in human breast cancer.ID4 is the most recently discovered member of the Inhibitor of DNA binding/Inhibitor of differentiation family of transcription factors. ID proteins contain a helix-loop-helix (HLH) domain enabling interaction with other basic helix-loop-helix (bHLH)-proteins. Via hetero-dimerisation with those transcription factors, ID
%U http://www.biomedcentral.com/1471-2407/8/154