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J. Biol. Chem., Vol. 282, Issue 16, 11732-11741, April 20, 2007

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Estrogen Receptor and the Activating Protein-1 Complex Cooperate during Insulin-like Growth Factor-I-induced Transcriptional Activation of the pS2/TFF1 Gene^*

Sylvain Baron, Aurélie Escande, Géraldine Albérola, Kerstin Bystricky, Patrick Balaguer, and Hélène Richard-Foy¹

From the Laboratoire de Biologie Moléculaire Eucaryote, UMR 5099 CNRS/Université Paul Sabatier, IFR109, 118 route de Narbonne, 31062 Toulouse, France and INSERM U540, 60 rue de Navacelles, 34090 Montpellier, France

Insulin like growth factor I (IGF-I) displays estrogenic activity in breast cancer cells. This activity is strictly dependent on the presence of estrogen receptor (ER). However the precise molecular mechanisms involved in this process are still unclear. IGF-I treatment induces phosphorylation of the AF1 domain of ER and activation of estrogen regulated genes. These genes are characterized by important differences in promoter architecture and response element composition. We show that promoter structure is crucial for IGF-I-induced transcription activation. We demonstrate that on a complex promoter such as the pS2/TFF1 promoter, which contains binding sites for ER and for the activating protein-1 (AP1) complex, transcriptional activation by IGF-I requires both ER and the AP1 complex. IGF-I is unable to stimulate transcription of an estrogen-regulated gene under the control of a minimal promoter containing only a binding site for ER. We propose a molecular mechanism with stepwise assembly of the AP1 complex and ER during transcription activation of pS2/TFF1 by IGF-I. IGF-I stimulation induces rapid phosphorylation and an increase in protein levels of the AP1 complex. Binding of the phosphorylated AP1 complex to the pS2/TFF1 promoter allows recruitment of the chromatin remodeling factor Brg1 followed by binding of ER via its interaction with c-Jun.

Received for publication, October 27, 2006 , and in revised form, February 17, 2007.

^* This work was supported by la Ligue Nationale Contre le Cancer, la Fondation pour la Recherche Médicale, l'Association pour la Recherche sur le Cancer, la Ligue du Tarn et Garonne, la Ligue Midi-Pyrénées, and l'Institut National du Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 33-561-33-59-40; Fax: 33-561-33-58-86; E-mail: hrfoy{at}ibcg.biotoul.fr.

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