title: Evidence of oncogene-induced senescence in thyroid carcinogenesis.
abstract: Oncogene-induced senescence (OIS) is a growth arrest triggered by the enforced expression of cancer-promoting genes and acts as a barrier against malignant transformation in vivo. In this study, by a combination of in vitro and in vivo approaches, we investigate the role of OIS in tumours originating from the thyroid epithelium. We found that expression of different thyroid tumour-associated oncogenes in primary human thyrocytes triggers senescence, as demonstrated by the presence of OIS hallmarks: changes in cell morphology, accumulation of SA-β-Gal and senescence-associated heterochromatic foci, and upregulation of transcription of the cyclin-dependent kinase inhibitors p16(INK4a) and p21(CIP1). Furthermore, immunohistochemical analysis of a panel of thyroid tumours characterised by different aggressiveness showed that the expression of OIS markers such as p16(INK4a), p21(CIP1) and IGFBP7 is upregulated at early stages, and lost during thyroid tumour progression. Taken together, our results suggest a role of OIS in thyroid carcinogenesis.
authors.affiliation: Molecular Mechanisms Unit, Department of Experimental Oncology and Molecular Medicine, IRCCS Foundation-Istituto Nazionale dei Tumori, Via G. Amadeo, 42 20133 Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Vizioli
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Possik
authors.forename: Eva
authors.initials: E
authors.lastname: Tarantino
authors.forename: Katrin
authors.initials: K
authors.lastname: Meissl
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Borrello
authors.forename: Claudia
authors.initials: C
authors.lastname: Miranda
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Anania
authors.forename: Sonia
authors.initials: S
authors.lastname: Pagliardini
authors.forename: Ettore
authors.initials: E
authors.lastname: Seregni
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peeper
authors.forename: Angela
authors.initials: A
authors.lastname: Greco
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011519:Proto-Oncogenes / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013961:Thyroid Gland / Q000166:cytology; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1