title: Circadian clock characteristics are altered in human thyroid malignant nodules.
abstract: BACKGROUND
  The circadian clock represents the body's molecular time-keeping system. Recent findings revealed strong changes of clock gene expression in various types of human cancers.
  
  
  OBJECTIVE
  Due to emerging evidence on the connection between the circadian oscillator, cell cycle, and oncogenic transformation, we aimed to characterize the circadian clockwork in human benign and malignant thyroid nodules.
  
  
  METHODS
  Clock transcript levels were assessed by quantitative RT-PCR in thyroid tissues. To provide molecular characteristics of human thyroid clockwork, primary thyrocytes established from normal or nodular thyroid tissue biopsies were subjected to in vitro synchronization with subsequent clock gene expression analysis by circadian bioluminescence reporter assay and by quantitative RT-PCR.
  
  
  RESULTS
  The expression levels of the Bmal1 were up-regulated in tissue samples of follicular thyroid carcinoma (FTC), and in papillary thyroid carcinoma (PTC), as compared with normal thyroid and benign nodules, whereas Cry2 was down-regulated in FTC and PTC. Human thyrocytes derived from normal thyroid tissue exhibited high-amplitude circadian oscillations of Bmal1-luciferase reporter expression and endogenous clock transcripts. Thyrocytes established from FTC and PTC exhibited clock transcript oscillations similar to those of normal thyroid tissue and benign nodules (except for Per2 altered in PTC), whereas cells derived from poorly differentiated thyroid carcinoma exhibited altered circadian oscillations.
  
  
  CONCLUSIONS
  This is the first study demonstrating a molecular makeup of the human thyroid circadian clock. Characterization of the thyroid clock machinery alterations upon thyroid nodule malignant transformation contributes to understanding the connections between circadian clocks and oncogenic transformation. Moreover, it might help in improving the thyroid nodule preoperative diagnostics.
authors: Department of Endocrinology, Diabetes, Nutrition, and Hypertension, University Hospital of Geneva, 4 Rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland. charna.dibner@hcuge.ch.
authors: Tiphaine
authors: T
authors: Mannic
authors: Patrick
authors: P
authors: Meyer
authors: Frederic
authors: F
authors: Triponez
authors: Marc
authors: M
authors: Pusztaszeri
authors: Gwendal
authors: G
authors: Le Martelot
authors: Olivia
authors: O
authors: Mariani
authors: Daniel
authors: D
authors: Schmitter
authors: Daniel
authors: D
authors: Sage
authors: Jacques
authors: J
authors: Philippe
authors: Charna
authors: C
authors: Dibner
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D002291:Carcinoma, Papillary; D021081:Chronobiology Disorders / Q000235:genetics / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D061251:Primary Cell Culture; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000503:physiopathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D016606:Thyroid Nodule / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D013965:Thyroidectomy; D059467:Transcriptome; D055815:Young Adult