Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations 英文参考文献.docVIP

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Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations 英文参考文献.doc

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Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations 英文参考文献

ProlactinReceptorinPrimaryHyperparathyroidism– Expression,FunctionalityandClinicalCorrelations FelixHaglund1,2*.,MingLu1.,VladanaVukojevic′2,3,Inga-LenaNilsson1,AdamAndreasson1,2, MensurDzˇabic′2,4,RobertBra¨nstro¨m1,AndersHo¨o¨g5,C.ChristoferJuhlin1,2,CatharinaLarsson1,2 1DepartmentofMolecularMedicineandSurgery,KarolinskaInstitutet,Stockholm,Sweden,2CenterforMolecularMedicine,KarolinskaInstitutet,Stockholm,Sweden, 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, 4Department of Medicine-Solna, Karolinska Institutet, Stockholm, Sweden, 5DepartmentofOncology-Pathology,KarolinskaInstitutet,Stockholm,Sweden Abstract Background:Primaryhyperparathyroidism(PHPT)isanendocrinedisordermostcommonlyaffectingwomen,suggestinga role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr)whichisassociatedwithtumoursofthebreastandotherorgans. Methodology/Principal Findings: PRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumoursanditsfunctionalityinculturedparathyroidtumourcells.Incomparisonwithothertissuesandbreastcancercells, high levels of prolactin receptor gene (PRLR) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/ 70kDawerehighlyexpressedinallparathyroidtumours.Inadditionvaryinglevelsofthe80kDaPRLrisoform,withknown proliferativeactivity,weredemonstrated.Inparathyroidtumours,PRLrimmunoreactivitywasobservedinthecytoplasm(in all cases, n=36), cytoplasmic granulae (n=16), the plasma membrane (n=12) or enlarged lysosomes (n=4). In normal parathyroid rim (n=28), PRLr was uniformly expressed in the cytoplasm and granulae. In in vitro studies of short-term culturedhumanparathyroidtumourcells,prolactinstimulationwasassociatedwithsignificanttranscriptionalchangesin JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover,PRLRgeneexpressioninparathyroidtumourswa