{'fraction_non_alphanumeric': 0.047976011994003, 'fraction_numerical': 0.025987006496751622, 'mean_word_length': 6.124555160142349, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Modulation of 17β‐Estradiol Signaling on Cellular Proliferation by Caveolin‐2

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. J. Cell. Physiol. 231: 1219–1225, 2016. © 2015 Wiley Periodicals, Inc.