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Rucaparib buy Expression of HDAC2 and ?3 was higher in poorly differentiated and hormone receptor negative tu mors, for HDAC2 we also found a significant correlation with HER2 overexpression. This correlation of HDACs and clincopathological parameters, which mark a more aggressive tumor type, was shown in other histological cancer types before. In accordance with our results other studies might also suggest a suppression of estrogen receptor by overexpression of HDAC. Several in vitro studies ana lyzed the reexpression of the estrogen receptor after therapy with Trichostatin A. Zhou et al. achieved a restoring of estrogen receptor mRNA and protein expression. These findings suggest that estrogen receptor could be suppressed by enhanced HDAC activ ity and restored by HDAC inhibitors.

Additionally, multiple groups have analyzed the influ ence of HDAC inhibitors in estrogen receptor positive breast cancer. Here, treatment with HDAC inhibitors led to a down regulation of estrogen receptor alpha. In contrast, the estrogen receptor beta was shown to in crease the antiproliferative potential of HDAC inhibitors as well as apoptosis as analyzed by Duong et al. In clinical studies the combination of HDAC inhibitors and hormone therapy showed first effects. Munster et al. could show an response rate of 19% for the combination of Vorinostat and Tamoxifen In contrast, the mono therapy with Tamoxifen in metastatic breast cancer achieved only a response rate below 10%. Both, in vitro and in vivo studies show that HDAC2 could be a potential biomarker. Marchion et al.

showed the selective inhibition of HDAC2 in breast cancer cells to be responsible for hyperacetylation of histones and proteins. In clinical studies tumors with HDAC2 expression showed a more acetylated histone status after therapy with Doxorubicin and Vorinostat. HDAC2 might therefore mark tumors with response to HDAC inhibitors. In normal mammary gland, we saw a homogenous expression of the HDAC class I isoenzymes. Similar results are described by other groups. Despite our long observation time we could not observe any prognostic influence of the expression of any of the HDAC isoenzymes in this retrospective analyses. This could be due to the influ ence of variable therapy regimens in this time as well as the missing parameters of disease specific deaths. Other studies have described a prognostic role for HDAC1 in breast cancer.

Due to the staining on a TMA, a possible heterogeneously expression of the analysed iso enzymes could be underrepresented. Altogether, the interaction between the hormone re ceptor status and the HDAC expression as AV-951 well as HDAC inhibitors are complex and need to be evaluated in further studies. Conclusions As a conclusion, our results show that the class 1 HDAC isoenzymes 1, 2 and 3 are differentially expressed in breast cancer. HDAC2 and HDAC3 are strongly expressed in more aggressive tumor subtypes.

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