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. 2003 Feb 15;17(4):488–501. doi: 10.1101/gad.1051603

Figure 5.

Figure 5

Effect of p53 loss-of-function on the occurrence of tumor aneuploidy and tumor regression following abrogation of Wnt signaling. (A) Regression of MTB/TWNT tumors in the absence of p53. The size of biopsy-proven mammary tumors arising in chronically induced MTB/TWNT/p53(−/−) mice (n = 7) was monitored following doxycycline withdrawal. Regression curves for three representative tumors are shown. Tumors lacking p53 by germline transmission of two null alleles regressed with similar kinetics as tumors arising in mice with wild-type p53 alleles (cf. Figs. 5A and 3D). Tumor recurrence could not be assessed in p53(−/−) animals due to the rapid occurrence of lymphomas. (B) p53 loss of heterozygosity (LOH) in a subset of tumors arising in MTB/TWNT/p53(+/−) mice. Southern hybridization analysis was performed on genomic DNA derived from mammary tumors arising in mice inheriting a single null allele for p53. Selective loss of the wild-type p53 allele was apparent in a subset of these mammary tumors (lanes marked with *). (C) Correlation of tumor aneuploidy with p53 LOH. The ploidy of tumors arising in MTB/TWNT/p53(+/−) mice was determined by flow cytometric analysis of propidium iodide-stained nuclei. Representative DNA histograms for tumors without (left panels) and with (right panels) detectable p53 LOH by Southern analysis are shown. Aneuploidy was common in tumors with detectable p53 LOH (6 of 7 tumors, 86%), but rare in tumors without detectable p53 LOH (1 of 17 tumors, 6%). (D) Incomplete regression and regrowth of a subset of tumors arising in MTB/TWNT/p53(+/−) mice. The size of biopsy-confirmed mammary tumors arising in MTB/TWNT/p53(+/−) mice was monitored following doxycycline withdrawal as above. Regression curves for six representative tumors are shown. Unlike tumors arising in MTB/TWNT/p53(+/+) mice, which only rarely failed to regress completely following doxycycline withdrawal (2 of 35 tumors, 6%; see Fig. 3D), a substantial fraction of tumors arising in MTB/TWNT/p53(+/−) mice regressed incompletely following doxycycline withdrawal and resumed growth (12 of 30 tumors, 40%).