title: Histone deacetylase 6 regulates estrogen receptor alpha in uterine leiomyoma.
abstract: Histone deacetylase 6 (HDAC) 6 is a regulatory factor in the endocrine traffic network that controls growth factor receptor stability. Histone deacetylase 6 expression and its pathogenic role in the uterine leiomyoma have not been studied. Here, we demonstrated that there was a consistent pattern of increasing HDAC6 and estrogen receptor (ER) α expression in leiomyoma samples. For all individual cases, expression of HDAC6 in the normal myometrium or leiomyoma positively correlated with ERα expression. The spearman's rho (ρ) was .53 (P = .008) between HDAC6 and ERα in normal myometrium and, more significantly, the spearman rho was .80 (P < .001) between HDAC6 and ERα in leiomyoma. In ELT-3 leiomyoma cells, silencing HDAC6 expression substantially reduced ERα expression, lowered estrogen response, and inhibited ELT-3 cell growth. Our results, taken together, are the first to provide experimental evidence suggesting that HDAC6 may be an essential molecular therapeutic target in controlling leiomyoma growth.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Lin-Hung
authors.initials: LH
authors.lastname: Wei
authors.forename: Pao-Ling
authors.initials: PL
authors.lastname: Torng
authors.forename: Sheng-Mou
authors.initials: SM
authors.lastname: Hsiao
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
mesh_terms: D000328:Adult; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000201:enzymology / Q000378:metabolism*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012313:RNA; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases