In the present report, we investigated the action of retinoic acid (RA) on the transactivation of the epidermal growth factor receptor (EGFR) gene promoter. In a previous study, we showed that the estrogen receptor (ER) α activated by 17β-estradiol (E 2) increased EGFR expression by enhancing the binding of the transcription factor Sp1 to the EGFR minimal promoter in HeLa cells. Here, we demonstrate that ligand-activated RA receptor (RAR) α inhibited EGFR transactivation by competing with Sp1 for binding to the same promoter fragment in the same cell model. When RARα and ERα were coexpressed, the inhibitory effect of RA on transactivation of the EGFR promoter counteracted the enhancement induced by E 2-activated ERα and became more pronounced in the presence of ligand-free ERα. In the MCF7 breast cancer cell line, which endogenously expresses RARα and ERα, RA exerted anti-proliferative effects in the presence of ligand-free ERα. Moreover, interplay between the pathways mediated by the two receptors was observed, as RA counteracted E 2-induced cell proliferation. Our results suggest that the interference with the activity of Sp1 on the EGFR promoter could be related to the observed RA-mediated growth suppression of breast cancer cells. © 2011 Elsevier Masson SAS.

Action of retinoic acid receptor on EGFR gene transactivation and breast cancer cell proliferation: Interplay with the estrogen receptor / Salvatori, Luisa; Ravenna, Linda Ester; Francesca, Caporuscio; Principessa, Lorenzo; Coroniti, Giuseppe; Frati, Luigi; Russo, Matteo Antonio; Petrangeli, Elisa. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - STAMPA. - 65:4(2011), pp. 307-312. [10.1016/j.biopha.2011.03.007]

Action of retinoic acid receptor on EGFR gene transactivation and breast cancer cell proliferation: Interplay with the estrogen receptor

SALVATORI, Luisa;RAVENNA, Linda Ester;PRINCIPESSA, LORENZO;CORONITI, GIUSEPPE;FRATI, Luigi;RUSSO, Matteo Antonio;PETRANGELI, Elisa
2011

Abstract

In the present report, we investigated the action of retinoic acid (RA) on the transactivation of the epidermal growth factor receptor (EGFR) gene promoter. In a previous study, we showed that the estrogen receptor (ER) α activated by 17β-estradiol (E 2) increased EGFR expression by enhancing the binding of the transcription factor Sp1 to the EGFR minimal promoter in HeLa cells. Here, we demonstrate that ligand-activated RA receptor (RAR) α inhibited EGFR transactivation by competing with Sp1 for binding to the same promoter fragment in the same cell model. When RARα and ERα were coexpressed, the inhibitory effect of RA on transactivation of the EGFR promoter counteracted the enhancement induced by E 2-activated ERα and became more pronounced in the presence of ligand-free ERα. In the MCF7 breast cancer cell line, which endogenously expresses RARα and ERα, RA exerted anti-proliferative effects in the presence of ligand-free ERα. Moreover, interplay between the pathways mediated by the two receptors was observed, as RA counteracted E 2-induced cell proliferation. Our results suggest that the interference with the activity of Sp1 on the EGFR promoter could be related to the observed RA-mediated growth suppression of breast cancer cells. © 2011 Elsevier Masson SAS.
2011
egfr transactivation; estrogen receptor α; retinoic acid receptor α
01 Pubblicazione su rivista::01a Articolo in rivista
Action of retinoic acid receptor on EGFR gene transactivation and breast cancer cell proliferation: Interplay with the estrogen receptor / Salvatori, Luisa; Ravenna, Linda Ester; Francesca, Caporuscio; Principessa, Lorenzo; Coroniti, Giuseppe; Frati, Luigi; Russo, Matteo Antonio; Petrangeli, Elisa. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - STAMPA. - 65:4(2011), pp. 307-312. [10.1016/j.biopha.2011.03.007]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/422860
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact