Estrogen-dependent regulation of ornithine decarboxylase in breast cancer cells through activation of nongenomic cAMP-dependent pathways

Molecular Carcinogenesis
Chunhua QinStephen Safe

Abstract

17beta-estradiol (E2) induces ornithine decarboxylase (ODC) activity in several E2-responsive tissues/cells, and this study investigated the mechanism of hormone-induced transactivation in MCF-7 human breast cancer cells. E2-induced reporter gene (luciferase) activity in MCF-7 cells transfected with a construct (pODC1) containing the -164 to +29 region of the human ODC gene promoter linked to bacterial luciferase. This promoter sequence contains GC-rich Sp1 binding sites, CAAT, LSF, cAMP response element (CRE), and TATA motifs. Deletion and mutational analysis of the ODC promoter showed that both CAAT and LSF sites were required for hormone-induced transactivation. Gel mobility shift and DNA footprinting assays indicated that NFYA and LSF bound the CAAT and LSF motifs, respectively, and GAL4-NFYA/GAL4-LSF chimeras were also activated by E2, 8-bromo-cAMP, and protein kinase A (PKA) expression plasmid. However, E2-induced transactivation of GAL4-NFYA and GAL4-LSF was blocked by the PKA inhibitor SQ22356 indicating that the mechanism of ODC induction by E2 involves upregulation of cAMP/PKA through nongenomic pathways of estrogen action.

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Citations

Jun 27, 2007·Breast Cancer Research and Treatment·Ellis R Levin, Richard J Pietras
Feb 12, 2005·Molecular Endocrinology·Ellis R Levin
Feb 13, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Vu Hoang DangEui-Bae Jeung
Jan 18, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Xiangrong LiStephen Safe
Sep 6, 2005·Differentiation; Research in Biological Diversity·Ildikó LoikkanenSeppo Vainio
Dec 1, 2010·Toxicological Research·Eui-Bae Jeung, Kyung-Chul Choi
Jul 15, 2015·Journal of Molecular Biology·Leonor Miller-FlemingMarkus Ralser
Mar 28, 2008·American Journal of Physiology. Cell Physiology·Liu Hua WeiLouis J Ignarro
Mar 21, 2007·Biochemical Society Transactions·B Grzelakowska-SztabertM Manteuffel-Cymborowska
Apr 29, 2006·Molecular Endocrinology·Ali PedramEllis R Levin
Feb 7, 2006·The Journal of Biological Chemistry·Anthony E Pegg
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Veena VijayanathanThresia Thomas
Mar 19, 2008·Journal of Proteome Research·Oriana E HawkinsWilliam H Hildebrand

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