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ΔNp73 overexpression induces oxaliplatin-resistance in colon cancer

AutorBonilla, Félix; Domínguez, Gemma
Fecha de publicación2015
EditorCSIC-UAM - Instituto de Investigaciones Biomédicas Alberto Sols (IIBM)
Citación2nd Symposium on Biomedical Research (2015)
Resumen[Background]: Aberrant expression of ΔNp73 has been associated with shorten cancer patient survival. We evaluate here whether this event could be due to the induction of drug resistance mechanisms. [Experimental Design]: HCT116 colon cancer cell line transfected with a vector containing ΔNp73 or a mock vector were treated with oxaliplatin and checked for the viability by MTT, Flow-citometry, TUNEL assay and Caspase-3 protein expression levels. Additionally, we determined in 77 colon cancer patients the expression of ΔNp73 and their putative target genes related with drug resistance ABCB1, HMGB1 and CASP1 by quantitative real-time RT-PCR. Disease-free survival (DFS) and overall survival (OS) were examined in each patient. [Results]: Ectopic expression of ΔNp73 significantly associated with a higher viability after oxaliplatin exposure. Positive correlations were observed between the expression levels of ΔNp73 variants and HMGB1. A trend was also observed for ABCB1. Overexpression of ΔNp73 isoforms predicted shortened OS (p = 0.05). High levels of ABCB1 and HMGB1 associated with shorter OS (p = 0.04 and p = 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (p = 0.008). [Conclusions]: The association of the upregulation of ΔNp73 with higher cancer cell viability after oxaliplatin treatment along with the fact that it could trigger HMG1 and ABCB1 in vivo, supports the hypothesis that the shorten survival observed in those cancer patients showing overexpression of ΔNp73 could be due to the induction of drug resistance processes by this isoform.
DescripciónResumen del póster presentado al 2nd Symposium on Biomedical Research: "Advances and perspectives in cancer", celebrado en Madrid el 17 de abril de 2015.-- et al.
Aparece en las colecciones: (IIBM) Comunicaciones congresos
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