HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Chiappetta, G. Articles by Viglietto, G. Search for Related Content PubMed PubMed Citation Articles by Chiappetta, G. Articles by Viglietto, G.

Laboratorio Oncologia Sperimentale III, Istituto Nazionale Tumori, via M. Semmola, 80131 Napoli, Italy
¹ Dipartimento di Biologia e Patologia Cellulare e Molecolare ‘L Califano’, Università Federico II, via S. Pansini 5, 80131 Napoli, Italy
² Dipartimento di Medicina Sperimentale e Clinica ‘G Salvatore’, Università Magna Graecia, Campus Universitario Germaneto, 88100 Catanzaro, Italy
³ Laboratorio di Oncologia Molecolare, BioGem scarl, Via Camporeale Area PIP, 83031 Ariano Irpino (AV), Italy
⁴ Hereditary Endocrine Cancer Group. Cancer Genetics Programme, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain
⁵ Dipartimento degli Studi e delle Istituzioni Territoriali, Università Parthenope, via Acton 38, 80131 Napoli, Italy

(Requests for offprints should be addressed to G Viglietto; Email: viglietto{at}unicz.it)

Loss of expression of the cyclin-dependent kinase inhibitor p27 through enhanced protein degradation frequently occurs in human cancer. Degradation of p27 requires ubiquitination by the S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of Skp1–Cullin–F-box protein ubiquitin ligases. In the present study, we have investigated the role of Skp2 in human thyroid tumours. Immunohistochemistry analysis showed that Skp2 was overexpressed significantly in thyroid carcinomas (26 out of 51) compared with goitres (0 out of 12, P<0.001) or adenomas (1 out of 10, P<0.05), and that high Skp2 expression was detected more often in anaplastic thyroid (ATC; 83%, n=12) than follicular thyroid (FTC; 40%, n=20) or papillary thyroid (PTC; 42%, n=19) carcinomas (P<0.05). Thyroid cancer cell lines and tissues with high levels of Skp2 protein presented high p27 degradation activity and there was an inverse correlation between Skp2 and p27 expression in thyroid cancer tissues (n=68; P<0.05). In most cases, the observed overexpression of Skp2 protein was paralleled by an increase in the levels of Skp2 mRNA, and we observed Skp2 gene amplification at 5p13 in 2 out of 6 cell lines and in 9 out of 23 primary tumours (six out of eight ATCs, two out of nine PTCs and one out of six FTCs) using Q-PCR and/or fluorescence in situ hybridization analysis. Finally, in vitro experiments demonstrated that suppression of Skp2 expression drastically reduced proliferation of thyroid cancer cells and, conversely, forced expression of Skp2 circumvented serum dependency and contact inhibition in Skp2-negative cells by promoting p27 degradation. These findings indicate that Skp2 plays an important role for the development of thyroid cancer.

This article has been cited by other articles:

				D. Yin, S. Ogawa, N. Kawamata, P. Tunici, G. Finocchiaro, M. Eoli, C. Ruckert, T. Huynh, G. Liu, M. Kato, et al. High-Resolution Genomic Copy Number Profiling of Glioblastoma Multiforme by Single Nucleotide Polymorphism DNA Microarray Mol. Cancer Res., May 1, 2009; 7(5): 665 - 677. [Abstract] [Full Text] [PDF]

				S. Uddin, M. Ahmed, P. Bavi, R. El-Sayed, N. Al-Sanea, A. AbdulJabbar, L. H. Ashari, S. Alhomoud, F. Al-Dayel, A. R. Hussain, et al. Bortezomib (Velcade) Induces p27Kip1 Expression through S-Phase Kinase Protein 2 Degradation in Colorectal Cancer Cancer Res., May 1, 2008; 68(9): 3379 - 3388. [Abstract] [Full Text] [PDF]