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Environ Health Perspect. May 2004; 112(7): 773–781.
PMCID: PMC1241992
Research Article

Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals.

Abstract

We developed a DNA microarray to evaluate the estrogen activity of natural estrogens and industrial chemicals. Using MCF-7 cells, we conducted a comprehensive analysis of estrogen-responsive genes among approximately 20,000 human genes. On the basis of reproducible and reliable responses of the genes to estrogen, we selected 172 genes to be used for developing a customized DNA microarray. Using this DNA microarray, we examined estrogen activity among natural estrogens (17beta-estradiol, estriol, estrone, genistein), industrial chemicals (diethylstilbestrol, bisphenol A, nonylphenol, methoxychlor), and dioxin. We obtained results identical to those for other bioassays that are used for detecting estrogen activity. On the basis of statistical correlations analysis, these bioassays have shown more sensitivity for dioxin and methoxychlor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adachi Tetsuya, Komiyama Masatoshi, Ono Yushin, Koh Kyu-Bom, Sakurai Kenichi, Shibayama Takako, Kato Masaki, Yoshikawa Tsutomu, Seki Naohiko, Iguchi Taisen, et al. Toxicogenomic effects of neonatal exposure to diethylstilbestrol on mouse testicular gene expression in the long term: a study using cDNA microarray analysis. Mol Reprod Dev. 2002 Sep;63(1):17–23. [PubMed]
  • Akutsu N, Bastien Y, Lin R, Mader S, White JH. Amphiregulin is a vitamin D3 target gene in squamous cell and breast carcinoma. Biochem Biophys Res Commun. 2001 Mar 9;281(4):1051–1056. [PubMed]
  • Astroff B, Safe S. Comparative antiestrogenic activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 6-methyl-1,3,8-trichlorodibenzofuran in the female rat. Toxicol Appl Pharmacol. 1988 Sep 30;95(3):435–443. [PubMed]
  • Beresford N, Routledge EJ, Harris CA, Sumpter JP. Issues arising when interpreting results from an in vitro assay for estrogenic activity. Toxicol Appl Pharmacol. 2000 Jan 1;162(1):22–33. [PubMed]
  • Branham WS, Fishman R, Streck RD, Medlock KL, De George JJ, Sheehan DM. ICI 182,780 inhibits endogenous estrogen-dependent rat uterine growth and tamoxifen-induced developmental toxicity. Biol Reprod. 1996 Jan;54(1):160–167. [PubMed]
  • Bulger WH, Muccitelli RM, Kupfer D. Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. Biochem Pharmacol. 1978;27(20):2417–2423. [PubMed]
  • Carlson David B, Perdew Gary H. A dynamic role for the Ah receptor in cell signaling? Insights from a diverse group of Ah receptor interacting proteins. J Biochem Mol Toxicol. 2002;16(6):317–325. [PubMed]
  • Das SK, Chakraborty I, Paria BC, Wang XN, Plowman G, Dey SK. Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus. Mol Endocrinol. 1995 Jun;9(6):691–705. [PubMed]
  • Demirpence E, Duchesne MJ, Badia E, Gagne D, Pons M. MVLN cells: a bioluminescent MCE-7-derived cell line to study the modulation of estrogenic activity. J Steroid Biochem Mol Biol. 1993 Sep;46(3):355–364. [PubMed]
  • Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863–14868. [PMC free article] [PubMed]
  • Fujimoto Takashi, Kitamura Shigeyuki, Sanoh Seigo, Sugihara Kazumi, Yoshihara Shin'ichi, Fujimoto Nariaki, Ohta Shigeru. Estrogenic activity of an environmental pollutant, 2-nitrofluorene, after metabolic activation by rat liver microsomes. Biochem Biophys Res Commun. 2003 Apr 4;303(2):419–426. [PubMed]
  • Gaido KW, Leonard LS, Maness SC, Hall JM, McDonnell DP, Saville B, Safe S. Differential interaction of the methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane with estrogen receptors alpha and beta. Endocrinology. 1999 Dec;140(12):5746–5753. [PubMed]
  • Green S, Walter P, Greene G, Krust A, Goffin C, Jensen E, Scrace G, Waterfield M, Chambon P. Cloning of the human oestrogen receptor cDNA. J Steroid Biochem. 1986 Jan;24(1):77–83. [PubMed]
  • Hu Yiding, Kupfer David. Enantioselective metabolism of the endocrine disruptor pesticide methoxychlor by human cytochromes P450 (P450s): major differences in selective enantiomer formation by various P450 isoforms. Drug Metab Dispos. 2002 Dec;30(12):1329–1336. [PubMed]
  • Hurbin Amandine, Dubrez Laurence, Coll Jean-Luc, Favrot Marie-Christine. Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines. J Biol Chem. 2002 Dec 20;277(51):49127–49133. [PubMed]
  • Inoue Akio, Hayashi Shin-ichi, Aoyagi Kazuhiko, Nishigaki Michiko, Sasaki Hiroki, Kiyama Ryoiti. A reporter gene assay for evaluation of tissue-specific responses to estrogens based on the differential use of promoters A to F of the human estrogen receptor alpha gene. J Pharmacol Toxicol Methods. 2002 May-Jun;47(3):129–135. [PubMed]
  • Inoue A, Yoshida N, Omoto Y, Oguchi S, Yamori T, Kiyama R, Hayashi S. Development of cDNA microarray for expression profiling of estrogen-responsive genes. J Mol Endocrinol. 2002 Oct;29(2):175–192. [PubMed]
  • Jacobs MN, Dickins M, Lewis DFV. Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (hERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):117–132. [PubMed]
  • Kanno Jun, Onyon Lesley, Peddada Shyamal, Ashby John, Jacob Elard, Owens William. The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single-dose studies. Environ Health Perspect. 2003 Sep;111(12):1550–1558. [PMC free article] [PubMed]
  • Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Res. 2000;2(5):335–344. [PMC free article] [PubMed]
  • Kitamura Shigeyuki, Ohmegi Motoko, Sanoh Seigo, Sugihara Kazumi, Yoshihara Shin'ichi, Fujimoto Nariaki, Ohta Shigeru. Estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes. Environ Health Perspect. 2003 Mar;111(3):329–334. [PMC free article] [PubMed]
  • Krishnamurthi K, Verbalis JG, Zheng W, Wu Z, Clerch LB, Sandberg K. Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5' leader sequence of the receptor mRNA. Endocrinology. 1999 Nov;140(11):5435–5438. [PubMed]
  • Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925–5930. [PMC free article] [PubMed]
  • Lapidus RG, Nass SJ, Davidson NE. The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia. 1998 Jan;3(1):85–94. [PubMed]
  • Ma L, de Roquancourt A, Bertheau P, Chevret S, Millot G, Sastre-Garau X, Espié M, Marty M, Janin A, Calvo F. Expression of amphiregulin and epidermal growth factor receptor in human breast cancer: analysis of autocriny and stromal-epithelial interactions. J Pathol. 2001 Aug;194(4):413–419. [PubMed]
  • McDonnell Donald P, Norris John D. Connections and regulation of the human estrogen receptor. Science. 2002 May 31;296(5573):1642–1644. [PubMed]
  • McDonnell Donald P, Wijayaratne Ashini, Chang Ching-yi, Norris John D. Elucidation of the molecular mechanism of action of selective estrogen receptor modulators. Am J Cardiol. 2002 Jul 3;90(1A):35F–43F. [PubMed]
  • McKenna Neil J, O'Malley Bert W. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002 Feb 22;108(4):465–474. [PubMed]
  • Nagel SC, Hagelbarger JL, McDonnell DP. Development of an ER action indicator mouse for the study of estrogens, selective ER modulators (SERMs), and Xenobiotics. Endocrinology. 2001 Nov;142(11):4721–4728. [PubMed]
  • Nickenig G, Bäumer AT, Grohè C, Kahlert S, Strehlow K, Rosenkranz S, Stäblein A, Beckers F, Smits JF, Daemen MJ, et al. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation. 1998 Jun 9;97(22):2197–2201. [PubMed]
  • Pons M, Gagne D, Nicolas JC, Mehtali M. A new cellular model of response to estrogens: a bioluminescent test to characterize (anti) estrogen molecules. Biotechniques. 1990 Oct;9(4):450–459. [PubMed]
  • Ray ME, Su YA, Meltzer PS, Trent JM. Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma. Oncogene. 1996 Jun 20;12(12):2527–2533. [PubMed]
  • Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett. 2001 Mar 31;120(1-3):1–7. [PubMed]
  • Shelby MD, Newbold RR, Tully DB, Chae K, Davis VL. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ Health Perspect. 1996 Dec;104(12):1296–1300. [PMC free article] [PubMed]
  • Spink DC, Lincoln DW, 2nd, Dickerman HW, Gierthy JF. 2,3,7,8-Tetrachlorodibenzo-p-dioxin causes an extensive alteration of 17 beta-estradiol metabolism in MCF-7 breast tumor cells. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6917–6921. [PMC free article] [PubMed]
  • Touyz RM, Berry C. Recent advances in angiotensin II signaling. Braz J Med Biol Res. 2002 Sep;35(9):1001–1015. [PubMed]
  • Vivacqua Adele, Recchia Anna Grazia, Fasanella Giovanna, Gabriele Sabrina, Carpino Amalia, Rago Vittoria, Di Gioia Maria Luisa, Leggio Antonella, Bonofiglio Daniela, Liguori Angelo, et al. The food contaminants bisphenol A and 4-nonylphenol act as agonists for estrogen receptor alpha in MCF7 breast cancer cells. Endocrine. 2003 Dec;22(3):275–284. [PubMed]
  • Watanabe Hajime, Suzuki Atsuko, Mizutani Takeshi, Khono Satomi, Lubahn Dennis B, Handa Hiroshi, Iguchi Taisen. Genome-wide analysis of changes in early gene expression induced by oestrogen. Genes Cells. 2002 May;7(5):497–507. [PubMed]
  • Yoshida T, Eguchi H, Nakachi K, Tanimoto K, Higashi Y, Suemasu K, Iino Y, Morishita Y, Hayashi S. Distinct mechanisms of loss of estrogen receptor alpha gene expression in human breast cancer: methylation of the gene and alteration of trans-acting factors. Carcinogenesis. 2000 Dec;21(12):2193–2201. [PubMed]
  • Yoshihara S, Makishima M, Suzuki N, Ohta S. Metabolic activation of bisphenol A by rat liver S9 fraction. Toxicol Sci. 2001 Aug;62(2):221–227. [PubMed]

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