Type 10 17β-hydroxysteroid dehydrogenase expression is regulated by C/EBPβ in HepG2 cells

The Journal of Steroid Biochemistry and Molecular Biology
Mirja RotinenIgnacio Encío

Abstract

17β-hydroxysteroid dehydrogenases (HSD17Bs) are enzymes that stereospecifically reduce or oxidize a keto- or hydroxy group at C17 of the steroid scaffold, respectively. Fourteen mammalian HSD17Bs have been identified so far. We previously described that the HSD17B8 gene is regulated by C/EBPβ in the hepatocarcinoma cell line HepG2. Here, we analyze the 5'-flanking region of 14 promoters (HSD17B1-14) looking for CCAAT boxes and binding sites for CCAAT enhancer binding factors (C/EBPs). All promoters were found to have binding sites for these transcription factors except HSD17B1. Ectopic expression of C/EBPα or C/EBPβ in HepG2 cells showed that HSD17B11 expression was induced by both transcription factors while HSD17B10 expression was only induced by C/EBPβ. The first 500bp of the 5'-flanking region of both genes contain two putative binding sites for C/EBPs. Gene reporter assays showed that C/EBPβ transactivated HSD17B10 but not HSD17B11. Additional experiments showed that several isoforms of C/EBPβ are involved in HSD17B10 regulation. Mutation of the CCAAT box located at -30/-19 induced HSD17B10 promoter activity when only LIP was expressed, while impaired LAP-induced HSD17B10 transactivation in HepG2 cells when LAP isoforms ar...Continue Reading

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Citations

Jul 11, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Song-Yu YangManfred Philipp
May 10, 2011·Molecular and Cellular Endocrinology·Mirja RotinenIgnacio Encío
Jan 23, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Bernhard ScheinerMattias Mandorfer
Mar 9, 2017·American Journal of Physiology. Endocrinology and Metabolism·Wen SuXiao-Yan Zhang
Oct 17, 2015·Molecular and Cellular Biochemistry·Tereza LundováVladimír Wsól

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