A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma

Giuliana Salvatore, Tito Claudio Nappi, Paolo Salerno, Yuan Jiang, Corrado Garbi, Clara Ugolini, Paolo Miccoli, Fulvio Basolo, Maria Domenica Castellone, Anna Maria Cirafici, Rosa Marina Melillo, Alfredo Fusco, Michael L. Bittner, Massimo Santoro

Research output: Contribution to journalArticle

Abstract

Here, we show that the anaplastic thyroid carcinoma (ATC) features the up-regulation of a set of genes involved in the control of cell cycle progression and chromosome segregation. This phenotype differentiates ATC from normal tissue and from well-differentiated papillary thyroid carcinoma. Transcriptional promoters of the ATC up-regulated genes are characterized by a modular organization featuring binding sites for E2F and NF-Y transcription factors and cell cycle-dependent element (CDE)/cell cycle gene homology region (CHR) cis-regulatory elements. Two protein kinases involved in cell cycle regulation, namely, Polo-like kinase 1 (PLK1) and T cell tyrosine kinase (TTK), are part of the gene set that is up-regulated in ATC. Adoptive overexpression of p53, p21 (CIP1/WAF1), and E2F4 down-regulated transcription from the PLK1 and TTK promoters in ATC cells, suggesting that these genes might be under the negative control of tumor suppressors of the p53 and pRB families. ATC, but not normal thyroid, cells depended on PLK1 for survival. RNAi-mediated PLK1 knockdown caused cell cycle arrest associated with 4N DNA content and massive mitotic cell death. Thus, thyroid cell anaplastic transformation is accompanied by the overexpression of a cell proliferation/genetic instability-related gene cluster that includes PLK1 kinase, which is a potential molecular target for ATC treatment.

Original languageEnglish
Pages (from-to)10148-10158
Number of pages11
JournalCancer Research
Volume67
Issue number21
DOIs
Publication statusPublished - Nov 1 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Salvatore, G., Nappi, T. C., Salerno, P., Jiang, Y., Garbi, C., Ugolini, C., Miccoli, P., Basolo, F., Castellone, M. D., Cirafici, A. M., Melillo, R. M., Fusco, A., Bittner, M. L., & Santoro, M. (2007). A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma. Cancer Research, 67(21), 10148-10158. https://doi.org/10.1158/0008-5472.CAN-07-1887