{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:01:11Z","timestamp":1774645271564,"version":"3.50.1"},"reference-count":47,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK066411"],"award-info":[{"award-number":["R01DK066411"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Murray-Heilig Fund in Molecular Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The protein product of the cyclin D1 oncogene functions by activating partner cyclin-dependent kinases (cdk)4 or cdk6 to phosphorylate, thereby inactivating, the retinoblastoma protein pRB. Nonclassical, cdk-independent, functions of cyclin D1 have been described but their role in cyclin D1-driven neoplasia, with attendant implications for recently approved cdk4\/6 chemotherapeutic inhibitors, requires further examination. We investigated whether cyclin D1\u2019s role in parathyroid tumorigenesis in vivo is effected primarily through kinase-dependent or kinase-independent mechanisms. Using a mouse model of cyclin D1\u2013driven parathyroid tumorigenesis (PTH-D1), we generated new transgenic lines harboring a mutant cyclin D1 (KE) that is unable to activate its partner kinases. While this kinase-dead KE mutant effectively drove mammary tumorigenesis in an analogous model, parathyroid-overexpressed cyclin D1 KE mice did not develop the characteristic biochemical hyperparathyroidism or parathyroid hypercellularity of PTH-D1 mice. These results strongly suggest that in parathyroid cells, cyclin D1 drives tumorigenesis predominantly through cdk-dependent mechanisms, in marked contrast with the cdk-independence of cyclin D1\u2013driven mouse mammary cancer. These findings highlight crucial tissue-specific mechanistic differences in cyclin D1\u2013driven tumorigenesis, suggest that parathyroid\/endocrine cells may be more tumorigenically vulnerable to acquired genetic perturbations in cdk-mediated proliferative control than other tissues, and carry important considerations for therapeutic intervention.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa159","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T22:22:20Z","timestamp":1599085340000},"source":"Crossref","is-referenced-by-count":5,"title":["CDK4\/6 Dependence of Cyclin D1\u2013Driven Parathyroid Neoplasia in Transgenic Mice"],"prefix":"10.1210","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-1693","authenticated-orcid":false,"given":"Jessica","family":"Costa-Guda","sequence":"first","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut"},{"name":"Center for 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