Human LBP-32/MGR is a Repressor of the P450scc in Human Choriocarcinoma Cell Line JEG-3

Henderson, Y.C.; Frederick, M.J.; Jayakumar, A.; Choi, Y.; Wang, M.T.; Kang, Y.; Evans, R.; Spring, P.M.; Uesugi, M.; Clayman, G.L.

doi:10.1016/j.placenta.2006.03.008

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Volume 28, Issue 2 , Pages 152-160, February 2007

Human LBP-32/MGR is a Repressor of the P450scc in Human Choriocarcinoma Cell Line JEG-3

Y.C. Henderson
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
M.J. Frederick
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
A. Jayakumar
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Y. Choi
- The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
M.T. Wang
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Y. Kang
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
R. Evans
- Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
P.M. Spring
- Department of Otolaryngology-Head & Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
M. Uesugi
- The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
G.L. Clayman
- Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
- Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
- Corresponding author. Department of Head & Neck Surgery, Unit 441, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Tel.: +1 713 792 6920; fax: +1 713 794 4662.

Accepted 8 March 2006. published online 28 May 2006.

Abstract

Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.

Keywords: LBP-32, Mammalian grainyhead, P450scc, JEG-3, Transcriptional repressor