Figure 5.

Bik loss, with or without Noxa loss, does not alter the pressure for selection for a mutated p53 pathway during Eμ-Myc-induced lymphoma development. (a) Genomic PCR analysis of the Ink4a/Arf locus revealed that none of the Eμ-Myc/Bik^−/− or Eμ-Myc/Bik^−/−Noxa^−/− lymphomas examined had a deletion in this gene. Controls include an Eμ-Myc lymphoma cell line known to contain a deletion in the Ink4a/Arf locus (denoted as –ve) and an Eμ-Myc lymphoma known to retain the Ink4a/Arf locus (denoted as +ve). (b) Representative western blots of p19^ARF, p53 and β-ACTIN (loading control) in randomly selected control Eμ-Myc, Eμ-Myc/Bik^−/− and Eμ-Myc/Bik^−/−Noxa^−/− lymphomas. Extracts from MEF immortalised with SV40 large T antigen were included as a positive control for p19^ARF and p53 overexpression. The Eμ-Myc lymphoma #280 was included on each blot as a reference lymphoma. (c) A graphical representation of the proportions of Eμ-Myc, Eμ-Myc/Bik^−/− and Eμ-Myc/Bik^−/−Noxa^−/− lymphomas analysed with a mutated p19^ARF–p53 pathway, as determined by western blotting for p53, p19^ARF protein. (d) Schematic diagram depicting activation of the p19^ARF–p53 pathway by c-MYC and the negative feedback loop that exists between p53 and p19^ARF