4.5 Article

HDAC1 and HDAC2 are Differentially Expressed in Endometriosis

期刊

REPRODUCTIVE SCIENCES
卷 19, 期 5, 页码 483-492

出版社

SAGE PUBLICATIONS INC
DOI: 10.1177/1933719111432870

关键词

endometriosis; endometrium; HDAC1; HDAC2; histone deacetylases; tissue microarray (TMA); ovarian steroid hormones; estrogen; progesterone

资金

  1. PSM RISE [R25 GM082406]
  2. National Institutes of Health [NIH-NICHD R01-HD050559, 3 R01 HD050559-04S1, NIH-MBRS S06-GM08239, NIH-NCI 1U56-CA126379-01, NIH-NIGMS R25 GM082406]
  3. [1F31 HD065431-01A1]
  4. [1F31 HD056964-01A1]

向作者/读者索取更多资源

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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