Abstract 3014: Implication of ΔNp73 isoform in drug resistance.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Aberrant expression of ▵Np73 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 ▵Np73 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 ▵Np73 significantly associated with a higher viability after oxaliplatin exposure. Positive correlations were observed between the expression levels of ▵Np73 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 ▵Np73 with higher cancer cell viability after oxaliplatin treatment along with the fact that it could trigger HMG1 and ABCB1 in vivo, supports the hyphotesis that the shorten survival observed in those cancer patients showing overexpression of ▵Np73 could be due to the induction of drug resistance processes by this isoform. Citation Format: Beatriz Soldevilla, Marta Rodriguez, Coral San Millan, Felix Bonilla, Gemma Dominguez. Implication of ΔNp73 isoform in drug resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3014. doi:10.1158/1538-7445.AM2013-3014