title: T3 enhances thyroid cancer cell proliferation through TRβ1/Oct-1-mediated cyclin D1 activation.
abstract: Several studies have demonstrated that thyroid hormone T3 promotes cancer cell growth, even though the molecular mechanism involved in such processes still needs to be elucidated. In this study we demonstrated that T3 induced proliferation in papillary thyroid carcinoma cell lines concomitantly with an up-regulation of cyclin D1 expression, that is a critical mitogen-regulated cell-cycle control element. Our data revealed that T3 enhanced the recruitment of the TRβ1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1 promoter, leading to its transactivation. In addition, silencing of TRβ1 or Oct-1 expression by RNA interference reversed both increased cell proliferation and up-regulation of cyclin D1, underlying the important role of both transcriptional factors in mediating these effects. Finally, T3-induced increase in cell growth was abrogated after knocking down cyclin D1 expression. All these findings highlight a new molecular mechanism by which T3 promotes thyroid cancer cell growth.
authors.affiliation: Centro Sanitario, University of Calabria, Rende, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Perri
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Catalano
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonofiglio
authors.affiliation: Centro Sanitario, University of Calabria, Rende, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Vizza
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rovito
authors.affiliation: Centro Sanitario, University of Calabria, Rende, Italy.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qi
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panza
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Rizza
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Lanzino
authors.affiliation: Dept. Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy; Centro Sanitario, University of Calabria, Rende, Italy. Electronic address: sebastiano.ando@unical.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D050811:Octamer Transcription Factor-1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014284:Triiodothyronine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt
keywords: CycD1; Oct-1; Octamer-transcription factor-1; T3; TH; TRs; TRβ1; Thyroid cancer; Thyroid hormone receptor β1; cyclin D1; thyroid hormone; thyroid hormone receptor β1; thyroid hormone receptors