The sex hormone 17β-estradiol (E2) exerts pleiotropic effects by binding to the ligand-activated transcription factor estrogen receptor α (ERα). The E2:ERα complex regulates several physiological processes, including cell survival and proliferation, through transcriptional effects (i.e., estrogen responsive element [ERE]-based gene transcription) and non-transcriptional membrane-initiated effects (i.e., the activation of extra-nuclear signaling cascades), which derive from the activation of the pool of ERα that is localized to plasma membrane caveolae. Caveolae are ω-shaped membrane sub-domains that are composed of scaffold proteins named caveolins (i.e., caveolin-1, caveolin-2, and caveolin-3). Although caveolin-3 is exclusively expressed in muscles, caveolin-1 and caveolin-2 are co-expressed in all human tissues. From a functional point of view, caveolin-2 can operate both dependently on and independently of caveolin-1, which is the main coat component of caveolae. Interestingly, while a functional interplay between caveolin-1 and ERα has been reported in the control of E2-induced physiological effects, the role of caveolin-2 in E2:ERα signaling within the cell remains poorly understood. This study shows that siRNA-mediated caveolin-2 depletion in breast ductal carcinoma cells (MCF-7) reduces E2-induced ERα phosphorylation at serine residue 118 (S118), controls intracellular receptor levels, precludes ERα-mediated extra-nuclear activation of signaling pathways, reduces ERα transcriptional activity, and prevents cellular proliferation. Meanwhile, the impact of caveolin-1 depletion on ERα signaling in MCF-7 cells is shown to be similar to that elicited by siRNA-mediated caveolin-2 depletion. Altogether, these data demonstrate that caveolin-2 expression is necessary for the control of E2-dependent cellular proliferation.

Totta, P., Gionfra, F., Busonero, C., & Acconcia, F. (2016). Modulation of 17β-Estradiol Signaling on Cellular Proliferation by Caveolin-2. JOURNAL OF CELLULAR PHYSIOLOGY [10.1002/jcp.25218].

Modulation of 17β-Estradiol Signaling on Cellular Proliferation by Caveolin-2.

TOTTA, PIERANGELA;GIONFRA, FABIO;BUSONERO, CLAUDIA;ACCONCIA, FILIPPO
2016

Abstract

The sex hormone 17β-estradiol (E2) exerts pleiotropic effects by binding to the ligand-activated transcription factor estrogen receptor α (ERα). The E2:ERα complex regulates several physiological processes, including cell survival and proliferation, through transcriptional effects (i.e., estrogen responsive element [ERE]-based gene transcription) and non-transcriptional membrane-initiated effects (i.e., the activation of extra-nuclear signaling cascades), which derive from the activation of the pool of ERα that is localized to plasma membrane caveolae. Caveolae are ω-shaped membrane sub-domains that are composed of scaffold proteins named caveolins (i.e., caveolin-1, caveolin-2, and caveolin-3). Although caveolin-3 is exclusively expressed in muscles, caveolin-1 and caveolin-2 are co-expressed in all human tissues. From a functional point of view, caveolin-2 can operate both dependently on and independently of caveolin-1, which is the main coat component of caveolae. Interestingly, while a functional interplay between caveolin-1 and ERα has been reported in the control of E2-induced physiological effects, the role of caveolin-2 in E2:ERα signaling within the cell remains poorly understood. This study shows that siRNA-mediated caveolin-2 depletion in breast ductal carcinoma cells (MCF-7) reduces E2-induced ERα phosphorylation at serine residue 118 (S118), controls intracellular receptor levels, precludes ERα-mediated extra-nuclear activation of signaling pathways, reduces ERα transcriptional activity, and prevents cellular proliferation. Meanwhile, the impact of caveolin-1 depletion on ERα signaling in MCF-7 cells is shown to be similar to that elicited by siRNA-mediated caveolin-2 depletion. Altogether, these data demonstrate that caveolin-2 expression is necessary for the control of E2-dependent cellular proliferation.
Totta, P., Gionfra, F., Busonero, C., & Acconcia, F. (2016). Modulation of 17β-Estradiol Signaling on Cellular Proliferation by Caveolin-2. JOURNAL OF CELLULAR PHYSIOLOGY [10.1002/jcp.25218].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11590/306633
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