Fig. 1: MCL-1 is required for MMTV-PyMT tumour maintenance in vivo.
From: Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function
A Diagram of experimental set-up for results presented in B, C. Female MMTV-PyMT mice were monitored until the largest tumour reached 5 mm diameter, induced with tamoxifen (day 0 on graph) for 4 consecutive days (to induce recombination in mice carrying RosaCRE-ERT2;Mcl1fl/+ alleles) and monitored until clinical endpoint. B Kaplan–Meier survival graph of mice WT for Mcl1 (n = 9) (median survival 18 days) and HET (n = 7) (median survival 23 days) post tamoxifen induction (P = 0.0424). Log-rank (Mantel–Cox) test. Genotypes of WT mice were 2× MMTV-PyMT;RosaCRE-ERT2;Mcl1+/+;RosaLSL-RFP, 4× MMTV-PyMT;Mcl1fl/+;RosaLSL-RFP and 3× MMTV-PyMT;Mcl1fl/fl;RosaLSL-RFP, genotypes of seven HET mice were MMTV-PyMT;RosaCRE-ERT2;Mcl1fl/+;RosaLSL-RFP. C Total tumour weight at endpoint of mice shown in B. WT (n = 9), HET (n = 7), n.s. not significant, unpaired t test. D Diagram of experimental set-up for results presented in E, F (see also Supplementary Fig. 1). Tumours were harvested from three ‘Mcl1WT’ (genotypes were MMTV-PyMT;RosaCRE-ERT2;Mcl1+/+;RosaLSL-RFP/MMTV-PyMT;Mcl1fl/+;RosaLSL-RFP/MMTV-PyMT;Mcl1fl/fl;RosaLSL-RFP) and 3 ‘Mcl1fl/fl’ (genotypes were 2× MMTV-PyMT;RosaCRE-ERT2;Mcl1fl/fl;RosaLSL-RFP and 1× MMTV-PyMT;RosaCRE-ERT2;Mcl1fl/fl) donor mice and tumour fragments orthotopically transplanted into multiple FVB recipients (ten recipients of Mcl1WT fragments and nine recipients of Mcl1fl/fl fragments). Transplanted tumours were monitored until ~5 mm diameter before tamoxifen-induced CRE-ERT2 activation. E Change in tumour volume 3 weeks post Mcl1 deletion. Error bars represent mean ± SD, ***P = 0.0009 unpaired t test. Red dotted line indicates 100% of starting volume (i.e., no change). No Mcl1WT tumours regressed and 8/9 Mcl1fl/fl tumours regressed following CRE activation. F Kaplan–Meier survival curve of mice carrying tumours shown in (E). Median survival Mcl1WT 47 days, Mcl1fl/fl 91 days post tamoxifen induction P = 0.0022 Log-rank (Mantel–Cox) test.
