Evidence of oncogene-induced senescence in thyroid carcinogenesis

Maria Grazia Vizioli, Patricia A. Possik, Eva Tarantino, Katrin Meissl, Maria Grazia Borrello, Claudia Miranda, Maria Chiara Anania, Sonia Pagliardini, Ettore Seregni, Marco A. Pierotti, Silvana Pilotti, Daniel S. Peeper, Angela Greco

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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.

Original languageEnglish
Pages (from-to)743-757
Number of pages15
JournalEndocrine-Related Cancer
Volume18
Issue number6
DOIs
Publication statusPublished - Dec 2011

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ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Vizioli, M. G., Possik, P. A., Tarantino, E., Meissl, K., Borrello, M. G., Miranda, C., Anania, M. C., Pagliardini, S., Seregni, E., Pierotti, M. A., Pilotti, S., Peeper, D. S., & Greco, A. (2011). Evidence of oncogene-induced senescence in thyroid carcinogenesis. Endocrine-Related Cancer, 18(6), 743-757. https://doi.org/10.1530/ERC-11-0240