HDAC1 and HDAC2 are differentially expressed in endometriosis

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This study found that HDAC1 and HDAC2 gene and protein expression differ between endometriotic and normal endometrial cells and tissues, with altered hormone regulation in endometriotic cells.

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This study assessed basal and hormone-regulated expression of histone deacetylases HDAC1 and HDAC2 in endometriotic cell lines and in human tissues, using quantitative PCR in cells and tissues and immunohistochemistry on an endometriosis tissue microarray. Basal HDAC1/2 gene expression was significantly higher in endometriotic versus endometrial stromal cells (confirmed by Western blot), and estradiol and progesterone differentially modulated HDAC1/2 in endometrial epithelial or stromal cells; however, steroid-hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed HDAC1/2 protein expression in a substantial proportion of patient lesions and endometrium, with expression varying by lesion localization. This paper is centrally about endometriosis — specifically, it reports differential expression and dysregulated hormone responsiveness of HDAC1 and HDAC2 in endometriosis.

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Abstract

Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormone-regulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue microarray (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 + P4 in endometrial stromal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs.
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Abstract

Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormone-regulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue micro-array (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 + P4 in endometrial stro-mal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs. Similar content being viewed by others

References

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Am J Obstet Gynecol. 2003;189(1):280–294. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Colón-Díaz, M., Báez-Vega, P., García, M. et al. HDAC1 and HDAC2 are Differentially Expressed in Endometriosis. Reprod. Sci. 19, 483–492 (2012). https://doi.org/10.1177/1933719111432870 Published: Issue date: DOI: https://doi.org/10.1177/1933719111432870

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endometriosis

MeSH descriptors

Endometriosis Gene Expression Histone Deacetylase 1 Histone Deacetylase 2 Cell Line Endometriosis Endometrium Endometrium Epigenesis, Genetic Female Gastrointestinal Diseases Gastrointestinal Diseases Gene Expression Regulation Gene Expression Regulation Histone Deacetylase 1 Histone Deacetylase 1 Histone Deacetylase 2 Histone Deacetylase 2 Hormones Hormones

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