A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma

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. Transcri...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2007-11, Vol.67 (21), p.10148-10158
Main Authors: SALVATORE, Giuliana, CLAUDIO NAPPI, Tito, MELILLO, Rosa Marina, FUSCO, Alfredo, BITTNER, Michael L, SANTORO, Massimo, SALERNO, Paolo, YUAN JIANG, GARBI, Corrado, UGOLINI, Clara, MICCOLI, Paolo, BASOLO, Fulvio, DOMENICA CASTELLONE, Maria, CIRAFICI, Anna Maria
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Carcinoma - genetics
Carcinoma - pathology
Cell Cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - physiology
Cell Proliferation
Chromosomal Instability
Endocrinopathies
Humans
Malignant tumors
Medical sciences
Pharmacology. Drug treatments
Polo-Like Kinase 1
Promoter Regions, Genetic
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - physiology
Protein-Tyrosine Kinases
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Thyroid Neoplasms - genetics
Thyroid Neoplasms - pathology
Thyroid. Thyroid axis (diseases)
Tumor Suppressor Protein p53 - physiology
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-07-1887