Expression profile of class I histone deacetylases in human cancer tissues

Abstract

Abstract. Histone deacetylase (HDAC) activity is one of the widely used and well-established mechanisms for regulation of various genes in cancer. To identify which subtype of class I HDACs are overexpressed in cancers, we analyzed the expression of class I HDAC isotypes composed of HDAC1, 2, 3 and 8 in several cell lines and human cancer tissues, including cancer of the stomach, esophagus, colon, prostate, breast, ovary, lung, pancreas and thyroid. The results showed that >75% of human cancer tissues and their corresponding non-cancerous epithelium showed high expression of these class I HDACs. However, the immunoreactivity of HDAC8 in both prostatic cancer tissue and non-cancerous prostate glands was lower than that in other cancer tissues. Furthermore, 5-40% of cancer tissues overexpressed class I HDACs, when compared with normal epithelium. The results suggest the potential usefulness of HDAC inhibitors for the treatment of a wide variety of human cancers.

HDACs and HDAC inhibitors in colon cancer

“…[57][58][59][60]62 Most of these studies have reported increased expression of the class I HDACs, HDAC1, 57,59,62,63 HDAC2, 57,60,62,63 HDAC3 57 and HDAC8, 57,58,60,62 in colon tumors relative to adjacent normal mucosa. Increased expression of HDACs 1, 2 and 8 in colon tumors has been demonstrated at both the protein and mRNA level, suggesting transcriptional activation may be a likely mechanism of overexpression.…”

“…[57][58][59][60] The class I HDACs, 1, 2, 3 and 8, 52,57 and the class II HDAC, HDAC4 (Wilson and Mariadason, unpublished), are expressed in the normal colon and small intestine and primarily in the proliferating crypt compartment. The expression of HDACs 5, 6, 7, 9 and 10 in normal colon has not been reported.…”

Discovery of N-hydroxy-4-(3-phenylpropanamido)benzamide derivative 5j, a novel histone deacetylase inhibitor, as a potential therapeutic agent for human breast cancer

“…5j exhibited good antiproliferative activities against a broad spectrum of human cancer cell lines especially for breast cancer. Based on the HDAC inhibition effects by 5j, a panel of human tumor cell lines comprised of highly expressed class I HDACs 15 were selected to be treated with various concentrations of inhibitors in vitro. The antiproliferative activity was detected by MTT assay.…”

“…Over 50% percent, or 800,000 cases, occur in women in Asia. HDACs was found predominantly expression in breast carcinoma, 15 and some reports have demonstrated that HDAC1 and 3 but not HDAC8 are upregulated, and repressed tumor suppressor gene ARHI in breast cancers, 26 HDAC1, HDAC2 and HDAC6 are decreased with breast cancer tumor progression, and histone H4 acetylation is decreased during breast cancer progression from normal epithelium to invasive cancer. 27 HDAC s such as SAHA has been shown to induce growth arrest, differentiation and apoptosis in human breast cancer cell lines 8,9 as well as some other HDACis such as TSA, PXD101 and CHAPs.…”

Matrine Reduces Proliferation of Human Lung Cancer Cells by Inducing Apoptosis and Changing miRNA Expression Profiles

“…In the repression of gene transcription expression, histone deacetylases (HDACs) play a significant role by changing chromatin structure (Thiagalingam et al, 2003) and affecting proliferation, cell cycling, apoptosis, differentiation, DNA replication, DNA damage response and migration of cancer cells (Langer et al, 2010;Li et al, 2013a). It has been reported that over-expression of HDACs has been detected in lung cancer tissues (Sasaki et al, 2004;Krusche et al, 2005;Nakagawa et al, 2007;Fritzsche et al, 2008;Weichert et al, 2008a;Weichert et al, 2008b;Kallsen et al, 2012) and that the expression of HDAC promotes the progress of lung cancer (Zhang et al, 2012b). Specifically, the expression of HDAC1 is related to advanced non small cell lung cancers (NSCLCs) (Minamiya et al, 2011), and an independent predictor of poor prognosis in patients with NSCLC (Bremnes et al, 2006).…”