title: Human endometrial cytodifferentiation by histone deacetylase inhibitors.
abstract: Abstract Human uterine endometrium repeats proliferation, differentiation (decidualization) and tissue breakdown during the menstrual period. Appropriate secretion of ovarian steroid hormones regulates these sequential endometrial remodeling cycles. While progesterone replacement therapy is adopted for endometrial dysfunction of differentiation, including recurrent impairment of implantation, no obvious effective results are obtained. Histone reversible acetylation, regulated by histone acetyltransferases and histone deacetylases plays a pivotal role in gene transcription. Although, in cells cultured with histone deacetylase inhibitors (HDACI), the expression of only about 2% of expressed genes is changed twofold or more compared with untreated control cells. Numerous previous works have demonstrated that HDACI affect cell proliferation/apoptosis in a variety of types of cells. To date, several HDACI are in phase I or phase II clinical trials as anticancer drugs. However, no reports have been found that HDACI is useful for transdifferentiation in human endometrium. Recently, we reported that HDACI could induce the expression of differentiation marker proteins, morphological change and functional cytodifferentiation in both human endometrial stromal and epithelial cells. In this review, we summarize the effect of HDACI against the human endometrial cytodifferentiation, indicating the possibility that HDACI can be used not only as an anticancer drug, but also as a transdifferentiation reagent, based on a new strategy.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku, Tokyo, Japan. uchida@sc.itc.keio.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maruyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Masuda
authors.forename: Toru
authors.initials: T
authors.lastname: Arase
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sugiura
authors.forename: Maki
authors.initials: M
authors.lastname: Onouchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajitani
authors.forename: Hironori
authors.initials: H
authors.lastname: Asada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004717:Endometrium / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014591:Uterine Diseases / Q000188:drug therapy; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000071816:Glycodelin; D006023:Glycoproteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C045246:PAEP protein, human; D011257:Pregnancy Proteins; C012589:trichostatin A; D000077337:Vorinostat; D006655:Histone Deacetylases