Correlation of gene expression and relative copy number of SIAH2 in basal like tumors A cohort of familial tumors, which included 15 basal like tumors, was previously analyzed on the basis of gene expression and copy number analysis. The 15 basal like tumors showed a significant correlation www.selleckchem.com/products/PD-0332991.html between SIAH2 expression and estimated copy number. Two of the 15 basal like tumors showed a copy number gain and a further three of 15 basal like tumors showed loss of heterozygosity at this region. In contrast, 15 non basal like tumors did not show any copy number Inhibitors,Modulators,Libraries change in this region. Relationship between SIAH2 expression and relapse free and overall survival There was no correlation present between SIAH2 expression and overall relapse free survival in DCIS only patients.

Although there was a significantly shorter relapse Inhibitors,Modulators,Libraries free survival in all patients with invasive carcinomas Inhibitors,Modulators,Libraries stratified by SIAH2, no significant association with relapse free survival was observed in univariate analysis in different breast cancer intrinsic groups stratified by SIAH2. There was also no significant association between SIAH2 in invasive carcinomas of all patients and relapse free survival in multivariate analysis. Discussion Hypoxia is a pivotal driver in Inhibitors,Modulators,Libraries breast tumor progression, leading to transcription of several suites of genes involved in angiogenesis, cell survival, cell proliferation and an enhanced metastatic Inhibitors,Modulators,Libraries phenotype that are advanta geous to the neoplastic cells. SIAH2 is part of the ubiquitin ligase complex that target proteins for protea somal degradation and enhances HIF 1a expression by reducing the abundance of the prolyl hydroxylases.

These enzymes, in the absence of SIAH2, hydro xylate prolyl residues in the oxygen dependent domain of HIF 1a, resulting in HIF 1a proteasomal degradation sellckchem and attenuation of the hypoxic response. Since SIAH2 has the potential to profoundly influence the hypoxic response, we investigated its expression in normal and neoplastic breast tissues. We observed significant upregulation of SIAH2 in the nucleus in the transition from normal to in situ and invasive carcinomas in breast cancer, supporting the notion of an important role of SIAH2 in breast cancer progression. SIAH2 has a nuclear localization signal that could account for its subcellular pattern of expression. The increase in SIAH2 in in situ and invasive car cinomas correlates with the hypoxia that occurs in neo plasia as the metabolic demand of the tumor exceeds the supply of nutrients and oxygen from the disordered vasculature that is developing. Correlation analysis showed a significant relationship between high levels of breast tumor SIAH2, negative ER and PR and high HER2.