Survivin regulates expression of p73 isoforms TAp73 and ΔNp73 in colon cancer cell lines with and without γ-radiation
(English)Manuscript (Other academic)
Wild type p53 represses expression of survivin, however little is known if survivin regulates p53 and the two isoforms of the p53 homologue p73, TAp73 and ΔNp73. The aim of our study was to investigate a possible connection between survivin and TAp73 and ΔNp73 in colon cancer cell lines HCT-116p53+/+ and HCT- 116p53-/- with and without γ-irradiation. HCT-116p53+/+ and HCT-116p53-/- were transfected with either survivin cDNA or siRNA against survivin. Cells transfected with siRNA were irradiated with 0Gy or 4Gy γ-irradiation to induce DNA-damage. Expression levels of survivin, TAp73, ΔNp73, mRNA and protein, and p53 protein was measured by RT-PCR and Western blot. Apoptosis was measured by means of M30- Apoptosense™ Elisa. Over-expression of survivin did not significantly change TAp73 or ΔNp73 mRNA and protein, whilst wild type p53 decreased. When survivin was knocked down, mRNA and protein of TAp73 and ΔNp73 decreased, both with and without γ-irradiation. Knockdown of survivin increased apoptosis in both HCT-116 cell lines with and without γ-irradiation. Knockdown of survivin decreased levels of TAp73 and ΔNp73 in both HCT-116p53+/+ and HCT-116p53-/-, and caused an increase in apoptosis, especially noticeable in HCT-116p53-/- after irradiation. Survivin down-regulation did not seem to affect the levels of wild type p53, whilst an up-regulation of survivin down-regulated wild type p53.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-18431OAI: oai:DiVA.org:liu-18431DiVA: diva2:219164