Apicidin suppresses transcription of 17 beta-hydroxysteroid dehydrogenase type 1 in endometrial adenocarcinoma cells

Keles E., Lianeri M., Jagodzinski P. P.

MOLECULAR BIOLOGY REPORTS, vol.38, no.5, pp.3355-3360, 2011 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 5
  • Publication Date: 2011
  • Doi Number: 10.1007/s11033-010-0441-3
  • Journal Name: MOLECULAR BIOLOGY REPORTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3355-3360
  • Keywords: HSD17B1, Apicidin, Endometrial cancer, HISTONE DEACETYLASE INHIBITOR, GENE-EXPRESSION, CANCER-CELLS, HUMAN BREAST, DEHYDROGENASE, ESTROGEN, ACTIVATION, INVOLVEMENT, ENDOCRINE, INDUCTION
  • Gazi University Affiliated: No

Abstract

It has recently been reported that endometrial cancer cells are able to convert estron (E1) to 17 beta estradiol (E2). We observed the presence of 17 beta-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.