HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0134v1 200/1/85    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rotinen, M. Articles by Villar, J. Search for Related Content PubMed PubMed Citation Articles by Rotinen, M. Articles by Villar, J.

Department of Health Sciences, Universidad Pública de Navarra, Avda. Barañain, 31008 Pamplona, Spain

(Correspondence should be addressed to J Villar who is now at National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA; Email: villarj{at}mail.nih.gov)

^* (M M Alonso is now at the Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.)

Hydroxysteroid (17-beta) dehydrogenase (HSD17B) are the enzymes responsible for the reversible interconversion of 17-hydroxy and 17-keto steroids. The human and mouse type 8 17β-HSD (HSD17B8) selectively catalyze the conversion ofestradiol (E2) to estrone (E1). We previously described thatHSD17B8 is transcriptionally regulated by C/EBPβ, andthat C/EBPβ is bound to CCAAT boxes located at –5 and –46 of the transcription start site in basal conditions in HepG2 cells. Furthermore, ectopic expression of C/EBPβ transactivated the HSD17B8 promoter activity. Here, we show that HSD17B8 expression is up-regulated in response toE2 in the estrogen receptor (ER) positive MCF-7 cells. Results showed that this induction is mediated by ER because i) E2 did not induce HSD17B8 expression in ERnegative HepG2 cells, ii) ectopic expression of ER restored E2-induced HSD17B8 expression, and iii) this induction wasblocked by the anti-ER ICI 182 780. Additional experiments showed that no estrogen response element was necessary for this regulation. However, the CCAAT boxes located at the HSD17B8 proximal promoter were required for E2-induced transcription. Furthermore, co-immunoprecipitation studies revealed tethering of ERtoC/EBPβ inresponse to E2 in cells expressing ER. Additionally, chromatin immunoprecipitation assays demonstrated that, in response to E2, ER is recruited to the CCAAT boxes in which C/EBPβ is already bound. Taken together, our results reveal that ER is involved in the transcriptional regulation of HSD17B8 gene in response to E2 through its interaction with C/EBPβ.