title: Apicidin suppresses transcription of 17β-hydroxysteroid dehydrogenase type 1 in endometrial adenocarcinoma cells.
abstract: It has recently been reported that endometrial cancer cells are able to convert estron (E1) to 17β estradiol (E2). We observed the presence of 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) transcript and protein in receptor positive ER(+) and negative ER(-) Ishikawa endometrial adenocarcinoma (ISH) cells. ER(+) ISH, but not ER(-)02 ISH, cells were significantly susceptible to apicidin induced death, and we further used ER(-)ISH cells to study the effect of apicidin on cellular levels of HSD17B1 transcript and protein. We showed that apicidin significantly lowered HSD17B1 transcript and protein levels in ISH cells. There was no significant effect on HSD17B1 transcript stability. However, chromatin immunoprecipitation analysis revealed that apicidin significantly decreased occupation of the first exon of the HSD17B1 gene by Polymerase II. Since intratumoral E1 to E2 conversion is a significant contributor to the progression of estrogen dependent cancers, and HDAC inhibitors are being tested in anticancer clinical trials, our observations may have clinical value.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781 Poznań, Poland.
authors.forename: Elif
authors.initials: E
authors.lastname: Keleş
authors.forename: Margarita
authors.initials: M
authors.lastname: Lianeri
authors.forename: Paweł Piotr
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology*; D020871:RNA Stability; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D011960:Receptors, Estrogen; C102351:apicidin; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase