{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:38Z","timestamp":1784557118327,"version":"3.55.0"},"reference-count":36,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>\n                    Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    ). [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the\n                    <jats:italic>CASR<\/jats:italic>\n                    mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous\n                    <jats:italic>FLNA<\/jats:italic>\n                    reduced\n                    <jats:italic>CASR<\/jats:italic>\n                    mRNA levels and total and membrane-associated CASR proteins. In agreement,\n                    <jats:italic>FLNA<\/jats:italic>\n                    mRNA levels positively correlated with\n                    <jats:italic>CASR<\/jats:italic>\n                    expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and\n                    <jats:italic>FLNA<\/jats:italic>\n                    transcript levels did not differ between PAds harboring 990R or 990G\n                    <jats:italic>CASR<\/jats:italic>\n                    variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the\n                    <jats:italic>CASR<\/jats:italic>\n                    expression levels. Loss of\n                    <jats:italic>FLNA<\/jats:italic>\n                    reduces\n                    <jats:italic>CASR<\/jats:italic>\n                    mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.\n                  <\/jats:p>","DOI":"10.1530\/jme-16-0184","type":"journal-article","created":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T22:20:27Z","timestamp":1479766827000},"page":"91-103","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":15,"title":["Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors"],"prefix":"10.1530","volume":"58","author":[{"given":"Alessandra","family":"Mingione","sequence":"first","affiliation":[{"name":"1Department of Health SciencesUniversity of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Verdelli","sequence":"additional","affiliation":[{"name":"2Laboratory of Experimental EndocrinologyIRCCS Istituto Ortopedico Galeazzi, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ferrero","sequence":"additional","affiliation":[{"name":"3Division of PathologyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vaira","sequence":"additional","affiliation":[{"name":"4Division of PathologyDepartment of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico and Istituto Nazionale Genetica Molecolare (INGM) Romeo ed Enrica Invernizzi, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"5Medical GeneticsIRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Scillitani","sequence":"additional","affiliation":[{"name":"6Endocrine UnitIRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Vicentini","sequence":"additional","affiliation":[{"name":"7Endocrine SurgeryIRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Balza","sequence":"additional","affiliation":[{"name":"8Internal Medicine UnitA.O. Alessandro Manzoni, Lecco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Beretta","sequence":"additional","affiliation":[{"name":"9Endocrine SurgeryIRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Terranegra","sequence":"additional","affiliation":[{"name":"10Sidra Medical and Research CenterDoha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Vezzoli","sequence":"additional","affiliation":[{"name":"11Nephrology and Dialysis UnitIRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Soldati","sequence":"additional","affiliation":[{"name":"1Department of Health SciencesUniversity of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Corbetta","sequence":"additional","affiliation":[{"name":"12Endocrinology ServiceDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017011617351624000_58.2.91.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100775200"},{"key":"2017011617351624000_58.2.91.2","unstructured":"Bondeson L Grimelius L De Lellis RA Lloyd R Akerstrom G Larsson C Arnold A Eng C Shane E Bilezikian JP 2004 Parathyroid carcinoma. In Pathology and Genetics. Tumors of Endocrine Organs. WHO Classification of Tumors, pp 128\u2013132. Eds DeLelli RA Lloyd RV Heltz PU C Eng. 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