Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF) properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC) harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR) treated SW480 cells expressing mutant p53 R273H (GEO#: GSE77533). We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.
Bibliographical noteFunding Information:
We acknowledge the Director, National Institute of Biomedical Genomics, Kalyani, India for kindly providing the Illumina iScan facility. This work was supported by CSIR—Mayo Clinic Collaboration for Innovation and Translational Research Grant CMPP-08 and CSIR-NMITLI project TLP 0007 awarded to S. Roychoudhury. AD, PD and SKA are supported by predoctoral fellowship from the Council of Scientific and Industrial Research, India. SD is supported by postdoctoral fellowship from Department of Biotechnology (DBT), India.
© 2016 The Authors.
- Colorectal cancer
- Mutant p53