Disease relevance of ID4

• ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (P<0.0001), suggesting a potential mechanism of BRCA1 downregulation [1].
• Overall, our results have shown that transcriptional silencing of ID4 is related to the aberrant methylation of its promoter in gastric cancer [2].
• Based on our published microarray expression data, we noticed a prominent downregulation of ID4 in gastric adenocarcinoma [2].
• In clinical specimens from normal epithelia, adenomas, primary CRCs, and liver metastases, the frequency of ID4 hypermethylation was 0 of 9 (0%), 0 of 13 (0%), 49 of 92 (53%), and 19 of 26 (73%), respectively, with a significant elevation according to CRC pathological progression [3].
• Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis [3].

High impact information on ID4

• ID4 mRNA level was suppressed in fully methylated cell lines [4].
• To determine its possible role, we examined epigenetic inactivation of ID4 gene by promoter hypermethylation in human breast cell lines and T1 breast cancer tissues [4].
• ID4 may play an important suppressive role in tumor progression, and its silencing by hypermethylation may increase the risk of regional lymph node metastasis [4].
• Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer [4].
• Methylation status of ID4 promoter CpG island was assessed by methylation-specific PCR (MSP); ID4 mRNA level was assessed by quantitative real-time RT-PCR [4].

Chemical compound and disease context of ID4

• In this study using bisulfite genomic sequencing, we have found hypermethylation of ID4 promoter in most gastric cancer cell lines and 30% of primary tumors [2].
• Restoration of ID4 expression in various gastric cancer cell lines was achieved by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone [2].

Biological context of ID4

• Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma [2].
• Furthermore, we have found significant association of ID4 promoter methylation with hMLH1 promoter methylation (P=0.008) and microsatellite instability (P=0.006) [2].
• EXPERIMENTAL DESIGN: In CRC cell lines, ID4 methylation status of the promoter region was assessed by methylation-specific PCR and bisulfite sequencing [3].
• CONCLUSIONS: ID4 gene is a potential tumor suppressor gene for which methylation status may play an important role in the CRC progression [3].
• cDNA cloning, tissue distribution and chromosomal localization of the human ID4 gene [5].

Anatomical context of ID4

• Northern blot analysis showed that ID4 is mainly expressed in thyroid, brain and fetal tissue and in some nervous system tumor cell lines [5].
• In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification [6].

Associations of ID4 with chemical compounds

• Methylmercury increased levels of expression of seven genes, including genes for ETV5 and ID4, and reduced those of two genes [7].

Other interactions of ID4

• An inverse association was observed between the mRNA expression of BRCA1 and ID4 (p = 0.024) and a negative correlation between their levels of expression (rs = -0.35 95% CI -0.59 a -0.04; p = 0.028) [8].
• Moreover, a negative correlation was stated between the level mRNAs of ER and ID4 (rs = - 0.45 95% CI -0.66 a -0.16; p = 0.0039) [8].
• The dense 5' CpG island covering the previously mapped upstream promoter of ID4 has prompted us to relate its downregulation to promoter hypermethylation [2].
• Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene [6].
• Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other [6].

Analytical, diagnostic and therapeutic context of ID4

• ID4 protein expression was assessed by immunohistochemistry analysis of tissue specimen [3].

References