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HDAC1 and HDAC2 are Differentially Expressed 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 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.

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Authors and Affiliations

  1. Department of Microbiology, Ponce School of Medicine and Health Sciences, PO Box 7004, Ponce, PR, 00731, USA

    Maricarmen Colón-Díaz BS, Perla Báez-Vega MT, Abigail Ruiz BS, Janice B. Monteiro PhD, Jessica Fourquet MPH & Idhaliz Flores PhD

  2. Hato Rey Pathology, Inc., San Juan, PR, USA

    Miosotis García MD

  3. Public Health Program, Ponce School of Medicine and Health Sciences, Ponce, PR, USA

    Manuel Bayona MD, PhD & Carolina Alvarez-Garriga MD DrPH

  4. Molecular Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Alexandra Achille MS & Edward Seto PhD

Authors
  1. Maricarmen Colón-Díaz BS
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  2. Perla Báez-Vega MT
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  3. Miosotis García MD
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  4. Abigail Ruiz BS
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  11. Idhaliz Flores PhD
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Correspondence to Idhaliz Flores PhD.

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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

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