Vol. 7, Issue 1, Part A (2025)

This research aimed to examine the impact of heightened histone deacetylase (HDAC) activity, which often leads to reduced acetylation in both chromatin-associated and cytoplasmic protein substrates. Such hypoacetylation can amend gene regulation and cellular functions, hypothetically contributing to carcinogenic changes. Though the participation of HDACs and acetylation in tumor ecology is well documented, their specific roles in the progression of breast cancer have not been sufficiently studied. This was assessed by evaluating the expression levels profiles of acetylated histone H4 (ac-H4), acetylated H4 at lysine 12 (ac-H4K12), and acetylated tubulin, as well as HDAC isoforms HDAC1, HDAC2, and HDAC6. The study utilized 22 lessening mammoplasty samples alongside 58 tissue samples comprising healthy breast epithelium, pre-invasive lesions (DCIS), and invasive ductal carcinoma (IDC). We employed nonparametric statistical tests to assess the variation in expression levels across these groups. Our findings revealed a marked decrease in histone acetylation since healthy breast epithelium to DCIS (P < 0.0001). Although DCIS and IDC generally showed comparable acetylation profiles, some cases exhibited further declines in ac-H4 and ac-H4K12 expression during the transition from DCIS to IDC. In addition, expression levels of HDAC1, HDAC2, and HDAC6 also declined, though to a lesser extent. Particularly, estrogen receptor-negative and high-grade tumors demonstrated more pronounced reductions in H4 acetylation and HDAC1 expression compared to their positive and lower-grade counterparts. In summary, our study indicates a consistent trend of decreasing acetylation during breast cancer headway from healthy tissue through DCIS to IDC. These findings highlight the potential of targeting hypoacetylation as a biomarker to evaluate the efficacy of HDAC inhibitors during the early stages of treatment.