title: Effects of ΔNp73β on cisplatin treatment in colon cancer cells.
abstract: p73 can activate transcription of p53-responsive genes, thereby inhibiting cell growth. An alternative promoter in the TP73 gene gives rise to an N-terminally truncated isoform of p73, ΔNp73, which lacks the transactivation domain of the full length TAp73 protein. TAp73 is considered pro-apoptotic, and ΔNp73 anti-apoptotic. In this study, we overexpressed ΔNp73β in p53 wild type and p53 mutant colon cancer cell lines and further exposed the cells to cancer therapeutic drug cisplatin. The results showed that cisplatin decreased the protein expression levels of ΔNp73β in a dose-dependent manner, and both TAp73 and p53 were upregulated after cisplatin treatment. Further, clonogenic potential and cell viability were decreased, and apoptotic cells increased, in p53 mutant and in p53 wild type cells. Cellular viability was significantly higher in ΔNp73β-cells than mock-transfected cells. However, ΔNp73β overexpression did not affect the cellular susceptibility to cisplatin. In conclusion, the overexpression of ΔNp73β increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of ΔNp73β in a dose-dependent manner.
authors.affiliation: Division of Tumor Biology, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Lööf
authors.forename: Daniella
authors.initials: D
authors.lastname: Pfeifer
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ding
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D002945:Cisplatin