Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas

Abstract

BACKGROUND

Class I histone deacetylases (HDACs) and acetylases (HATs) are members of transcriptional pre-initiation complexes assembled by steroid hormone receptors. Recently, HDAC inhibitors were shown to enhance differentiation of endometrial fibroblasts and endometrial adenocarcinomas. However, there is only rare information on HDAC and HAT expression in the human endometrium.

METHODS

HDAC-1, -2, -3 and HAT (PCAF and GCN5) mRNA expression was studied in tissue from premenopausal women undergoing hysterectomy by real-time or semiquantitative RT–PCR. HDAC protein expression was assessed by Western Blot and immunohistochemistry. In endometrial adenocarcinomas (n = 17), HDAC-1 expression was studied by immunohistochemistry.

RESULTS

In the human endometrium, HDAC-1, -2, -3 and PCAF mRNA are expressed without cyclical changes. Western blot analysis demonstrated that HDAC-2 protein expression was slightly, but significantly elevated in the secretory phase (P < 0.01 versus day 5–8), whereas HDAC-1 and -3 protein expression was constitutive throughout the menstrual cycle. By immunohistochemistry, nuclear expression of HDAC proteins was detected in all endometrial cell types. In the case of HDAC-3, immunostaining was significantly reduced in the endometrial surface epithelium on day 6–10 (P < 0.01 versus days 15–18 and 24–28). Compared to normal endometrium, a high proportion of endometrial adenocarcinomas showed impaired HDAC-1 protein expression in the epithelial and stromal compartment.

CONCLUSIONS

Class I HDACs and HATs are expressed in the human endometrium throughout the menstrual cycle, suggesting the cyclic endometrium as a potential target for HDAC inhibitors. We hypothesis that alterations of HDAC and/or HAT expression are potentially involved in impaired endometrial differentiation.

cancer, endometrium, histone deacetylases, steroid hormones, uterus