To investigate the estrogenic effects on the transcriptional regulation of the epidermal growth factor (EGF) receptor (EGFR) gene, we assayed its promoter ability to direct transcription of the luciferase reporter gene after transfection into HeLa cells. Our studies demonstrated a dose-dependent activation of the EGFR gene transcription by ligand-bound estrogen receptor alpha (ERalpha). This action was retained by the 36-bp core promoter fragment and did not require the receptor DNA binding domain, as demonstrated by analyzing the role of ERalpha deletion mutants on EGFR gene promoter-derived constructs. The 36-bp promoter fragment does not contain an estrogen response element but an imperfect thyroid hormone response element half-site that overlaps the Sp1 binding site. ERalpha does not bind this imperfect thyroid hormone response element half-site but is able to enhance binding of Sp1 to its site, in gel mobility shift assays, suggesting that the mechanism by which the receptor stimulated the transcription involved protein-protein interactions that replaced DNA binding. To explain this action, we propose a model in which induction of the EGFR gene expression by estrogens in HeLa cells is dependent upon the formation of a transcriptionally active ERalpha-Sp1 complex that binds to the GC-rich (Sp1) region of the minimal promoter.

Identification of an estrogen-mediated deoxyribonucleic acid-binding independent transactivation pathway on the epidermal growth factor receptor gene promoter / Salvatori, Luisa; Ravenna, Linda Ester; Felli, MARIA PIA; Cardillo, MARIA ROSARIA; Russo, Matteo Antonio; Frati, Luigi; Petrangeli, Elisa. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - STAMPA. - 141:(2000), pp. 2266-2274. [10.1210/en.141.6.2266]

Identification of an estrogen-mediated deoxyribonucleic acid-binding independent transactivation pathway on the epidermal growth factor receptor gene promoter.

SALVATORI, Luisa;RAVENNA, Linda Ester;FELLI, MARIA PIA;CARDILLO, MARIA ROSARIA;RUSSO, Matteo Antonio;FRATI, Luigi;PETRANGELI, Elisa
2000

Abstract

To investigate the estrogenic effects on the transcriptional regulation of the epidermal growth factor (EGF) receptor (EGFR) gene, we assayed its promoter ability to direct transcription of the luciferase reporter gene after transfection into HeLa cells. Our studies demonstrated a dose-dependent activation of the EGFR gene transcription by ligand-bound estrogen receptor alpha (ERalpha). This action was retained by the 36-bp core promoter fragment and did not require the receptor DNA binding domain, as demonstrated by analyzing the role of ERalpha deletion mutants on EGFR gene promoter-derived constructs. The 36-bp promoter fragment does not contain an estrogen response element but an imperfect thyroid hormone response element half-site that overlaps the Sp1 binding site. ERalpha does not bind this imperfect thyroid hormone response element half-site but is able to enhance binding of Sp1 to its site, in gel mobility shift assays, suggesting that the mechanism by which the receptor stimulated the transcription involved protein-protein interactions that replaced DNA binding. To explain this action, we propose a model in which induction of the EGFR gene expression by estrogens in HeLa cells is dependent upon the formation of a transcriptionally active ERalpha-Sp1 complex that binds to the GC-rich (Sp1) region of the minimal promoter.
2000
01 Pubblicazione su rivista::01a Articolo in rivista
Identification of an estrogen-mediated deoxyribonucleic acid-binding independent transactivation pathway on the epidermal growth factor receptor gene promoter / Salvatori, Luisa; Ravenna, Linda Ester; Felli, MARIA PIA; Cardillo, MARIA ROSARIA; Russo, Matteo Antonio; Frati, Luigi; Petrangeli, Elisa. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - STAMPA. - 141:(2000), pp. 2266-2274. [10.1210/en.141.6.2266]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/362083
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