Re cently, it has been suggested that alphaB crystallin pro motes tumor progression by enhancing endothelial cell survival, resulting in efficient tumor vascularization. There are several studies that introduce sHsps and especially Hsp27 and alphaB crystallin as contribu tors to the epithelial mesenchymal Trichostatin A buy transition process. Both proteins interact with the cytoskeleton and regulate its dynamic status by inducing mesenchymal like spindle cells. thus, they may promote cancer cell invasion and metastasis. Consequently, alphaB crystallin may contribute to an aggressive behavior Inhibitors,Modulators,Libraries of tumors. this is in line with our observation that alphaB crystallin is more commonly found in BCP and in those non TNBC that have a high histological grade and pro liferation rate.

Of note, in the current study the majority of non TNBC alphaB crystallin positive cases were Luminal B tumors, Inhibitors,Modulators,Libraries which by definition have a high Ki67 labeling index. The expression of alphaB crystallin in a subset of non TNBC has been mentioned by other stud ies, as well. BCP constitute a tumor subgroup associated with BRCA1 mutations. Tumors of patients with BRCA1 germ line mutations usually display the basal core phenotype. In this study we found that alphaB crystallin is as sociated with BCP and BRCA1 mutational status but not with BRCA1 protein expression. Moreover, no significant association was found between mutational status and pro tein expression. Despite the small sample size of BRCA1 mutant cases, this result is in line with the global view that IHC does not reliably reflect BRCA1 gene status and cannot be used for assessing the impact of BRCA1 protein expression on prognosis.

We also found a strong association between alphaB crystallin and p53 ex pression, which is again in line with BCP BRCA1 Inhibitors,Modulators,Libraries mu tant tumors. alphaB crystallin overexpression prevents apoptosis, through the interaction of the p53 down regu lated genes, such as bax or pro caspase3. Recently, it was shown that alphaB crystallin binds to p53 to se quester its translocation to the mitochondria during hydrogen peroxide Inhibitors,Modulators,Libraries induced apoptosis. Hence, like other Hsps, alphaB crystallin interacts with p53 and mod ulates its function. Inhibitors,Modulators,Libraries On the other hand, it is believed that p53 is involved in the regulation of Hsps in cancer and p53 mutations result in an increase of Hsp transcripts. Our IHC findings further support these interac tions, specifically between the alphaB crystallin and p53 sellckchem proteins. alphaB crystallin expression has been associated with poor clinical outcome in breast, head and neck and hepatocellular carcinoma. Moyano et al. found that this biomarker predicts for shorter disease specific survival, independent of other prognostic markers. By contrast, Chelouche Lev et al.