DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer

BMC Cancer

Javier Martinez-Useros²  Maria Rodriguez-Remirez²  Aurea Borrero-Palacios²  Irene Moreno²  Arancha Cebrian²  Teresa Gomez del Pulgar²  Laura del Puerto-Nevado²  Ricardo Vega-Bravo⁴  Alberto Puime-Otin⁴  Nuria Perez⁴  Sandra Zazo⁴  Clara Senin¹  Maria J Fernandez-Aceñero³  Maria S Soengas⁵  Federico Rojo⁴  Jesus Garcia-Foncillas² 

[1] Department of Oncology, Vigo Hospital, Vigo, Spain

[2] Translational Oncology Division, OncoHealth Institute, Health Research Institute - University Hospital “Fundación Jiménez Díaz”-UAM, Av. Reyes Católicos 2, 28040 Madrid, Spain

[3] Department of Pathology, Clinico San Carlos University Hospital, Madrid, Spain

[4] Department of Pathology, University Hospital “Fundación Jiménez Díaz”-UAM, Madrid, Spain

[5] Melanoma Research Group, Spanish National Cancer Research Centre, Madrid, Spain

关键词: KRAS;    Metastatic colorectal cancer;    Aggressive phenotype;    Irinotecan;    DEK;   

Others  :  1117865
DOI  :  10.1186/1471-2407-14-965

 received in 2014-10-14, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer.

Methods

Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment.

Results

The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type.

Conclusions

These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.

【 授权许可】

   
2014 Martinez-Useros et al.; licensee BioMed Central.

【 图 表 】

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