Increased expression of histone deacetylase 2 is found in human gastric cancer

Abstract

Accumulated evidence has established that aberrant regulation of histone deacetylases (HDACs) is one of the major causes of the development of human malignancies. Among different iso-enzymes of HDAC and sirtuins grouped as the HDAC super family, little is known as to how histone deacetylase 2 (HDAC2) causes carcinogenesis in solid tumors. Here, in order to investigate the possible role of HDAC2 in gastric carcinogenesis, we analyzed the expression of HDAC2 in 71 gastric adenocarcinomas by immunohistochemistry. Moderate to strong expression of HDAC2 was found in 44 (62%) out of a total of 71 tumors. The majority of positive tumors, which were detected in the nucleus but not in normal gastric epithelium, did not express HDAC2 or showed only weak positive staining. Interestingly, we also noted that HDAC2 expression appeared to be associated with tumor aggressiveness as HDAC2 expression was observed to be statistically significant in advanced gastric cancer (P=0.0023, Chi-square test) and in positive lymph node metastasis (P=0.0713, Chi-square test). Taken together, these results suggest that HDAC2 may play an important role in the aggressiveness of gastric cancer.

Selective Inhibition of Histone Deacetylases Sensitizes Malignant Cells to Death Receptor Ligands

“…Multiple HDAC enzymes have been identified, of which HDAC1 to HDAC10 are expressed in malignant cells (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). To understand the spectrum of HDACs inhibited by droxinostat and determine whether selective HDAC inhibition is sufficient to sensitize cells to FAS and TRAIL, we examined the spectrum of HDAC enzymes inhibited by droxinostat.…”

Development of an ELISA-Based HDAC Activity Assay for Characterization of Isoform-Selective Inhibitors

“…4 Among the metal-dependent HDAC isoforms, class I proteins are associated with cell-cycle progression, metastasis, and apoptosis, which are altered in cancers. As illustrative examples, increased expression of HDAC1 was observed in gastric, 5 colon, 6 prostrate, 7 and breast cancer, 8 while HDAC2 was overexpressed in gastric 9 and colorectal cancer. 10 Among the class II proteins, HDAC6 is overexpressed in oral squamous cell carcinoma and breast cancer tumors.…”

“…[5][6][7][8][9][10][11] Primary HDAC antibodies recognizing each of the isoforms were immobilized to different wells of a plate, followed by incubation with HeLa cell lysates to affix the respective HDAC isoform (Fig. 2).…”

The transforming growth factor beta-1 in the oncogenesis of human lung adenocarcinoma

“…В последнее время повышенное внимание уделяется метилированию и ацетилированию гистонов при лечении рака [41,42]. Диацелазы гистонов (histone deacetylases, HDACs) ча-сто сверхэкспрессированы при онкологических забо-леваниях, в последние годы они стали основной тера-певтической мишенью [43]. Повышенная экспрессия HDACs может привести к глушению транскрипции генов и аберрантной транскрипции из-за измененной экспрессии / мутации генов, кодирующих гистонаце-тилтрансферазу (HAT), HDAC-ферменты или их свя-зывающих партнеров, и тесно сопряжена с канцеро-генезом.…”