The FOXM1-PLK1 axis is commonly upregulated in oesophageal adenocarcinoma.

Dibb, M; Han, N; Choudhury, J; Hayes, S; Valentine, H; West, C; Ang, Y S; Sharrocks, A D

Dibb, M; Han, N; Choudhury, J; Hayes, S; Valentine, H; West, C; Ang, Y S; Sharrocks, A D.

Afiliación

Dibb M; Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.

Br J Cancer ; 107(10): 1766-75, 2012 Nov 06.

Article en En | MEDLINE | ID: mdl-23037713

RESUMEN

BACKGROUND: The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been shown to be overexpressed in a variety of different tumour types. METHODS: We have used a combination of RT-PCR, western blotting, tissue microarrays and metadata analysis of microarray data to study whether the FOXM1-PLK1 regulatory axis is upregulated and operational in oesophageal adenocarcinoma. RESULTS: FOXM1 and PLK1 are expressed in oesophageal adenocarcinoma-derived cell lines and demonstrate cross-regulatory interactions. Importantly, we also demonstrate the concomitant overexpression of FOXM1 and PLK1 in a large proportion of oesophageal adenocarcinoma samples. This co-association was extended to the additional FOXM1 target genes CCNB1, AURKB and CKS1. In a cohort of patients who subsequently underwent surgery, the expression of several FOXM1 target genes was prognostic for overall survival. CONCLUSIONS: FOXM1 and its target gene PLK1 are commonly overexpressed in oesophageal adenocarcinomas and this association can be extended to other FOXM1 target genes, providing potentially important biomarkers for predicting post-surgery disease survival.

Asunto(s)

Adenocarcinoma/genética; Proteínas de Ciclo Celular/genética; Neoplasias Esofágicas/genética; Factores de Transcripción Forkhead/genética; Proteínas Serina-Treonina Quinasas/genética; Proteínas Proto-Oncogénicas/genética; Adenocarcinoma/metabolismo; Proteínas de Ciclo Celular/biosíntesis; Proteínas de Ciclo Celular/metabolismo; Línea Celular Tumoral; Estudios de Cohortes; Neoplasias Esofágicas/metabolismo; Proteína Forkhead Box M1; Factores de Transcripción Forkhead/biosíntesis; Factores de Transcripción Forkhead/metabolismo; Regulación Neoplásica de la Expresión Génica; Humanos; Pronóstico; Proteínas Serina-Treonina Quinasas/biosíntesis; Proteínas Serina-Treonina Quinasas/metabolismo; Proteínas Proto-Oncogénicas/biosíntesis; Proteínas Proto-Oncogénicas/metabolismo; Regulación hacia Arriba; Quinasa Tipo Polo 1

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Adenocarcinoma / Proteínas Proto-Oncogénicas / Proteínas Serina-Treonina Quinasas / Proteínas de Ciclo Celular / Factores de Transcripción Forkhead Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Br J Cancer Año: 2012 Tipo del documento: Article Pais de publicación: Reino Unido

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