Figure 1: Loss of p120 induces multinucleation and chromosomal instability.
(a) Mammary-specific conditional female mice mutant for p120 and p53 (WAPcre;Ctnnd1F/F;Trp53F/F), E-cadherin and p53 (WAPcre;Cdh1F/F;Trp53F/F) or p53 alone (WAPcre;Trp53F/F) were stained for p120. Note the overt multinucleation in the p120 knockout mammary carcinoma cells (arrow) and the prominent influx of p120 expressing immune cells (macrophages; arrow head). Tissue architecture and nuclear morphology were visualized by H&E stainings. Scale bar, 50 μm. (b) Immunofluorescence (IF) imaging of cell lines (Trp53Δ/Δ-7, mILC-1 and PMC-1) derived from the corresponding tumours shown in a. Scale bar, 10 μm. (c) Quantification of bi- and multinucleation in the cell lines shown in b. Statistical significance was determined using the χ2-test. *P<0.05/‡P<0.05 (binucleation and multinucleation, respectively). (d) Control (-dox) and dox-treated (+dox) mouse and human cancer cell lines transduced with an inducible p120KD were stained for p120 and Lamin A/C. Scale bar, 10 μm. (e) Quantification of bi- and multinucleation of the p120-iKD cell lines shown in d over three consecutive passages in the absence or presence of dox. At least 200 control and dox-treated cells were analysed every passage. (f) Quantification of centrosome numbers in interphase PMC-1, Trp53Δ/Δ-7 p120-iKD and U2OS p120-iKD cells. Centrosome numbers were determined by IF staining for γ-tubulin. Statistical significance in c,e and f was determined using the χ2-test. *P<0.05/‡P<0.05 (binucleation and multinucleation respectively). NS, not significant.
