Extended Data Figure 7. Dose-dependent suppression of POLR2A inhibits tumorigenesis in POLR2A^loss, but not POLR2A^neutral tumours.

a, Quantification of POLR2A mRNA expression levels in subcutaneously xenografted HCT116 and SNU283 tumours expressing control or POLR2A shRNA (n = 5 mice per group). ** p < 0.01. Data are mean and s.d. b, Immunohistochemical staining of the aforementioned xenograft tumours. HE: haematoxylin and eosin. c, Cells positive for Ki67 (cell proliferation) or cleaved caspase-3 (apoptosis) per field and POLR2A expression in (b) were quantified. ** p < 0.01. n = 10 fields. Data are mean and s.d. d, Gross tumour images of xenograft tumours derived from subcutaneously implanted POLR2A^neutral and POLR2A^loss HCT116 cells (1 × 10⁶ cells injected). Both cell lines express control or Dox-inducible POLR2A shRNAs. After the initial establishment of tumours (100 mm³), mice were treated with (0.5, 1 and 2 μg ml⁻¹) Dox in drinking water. n = 5 mice per group. e, Quantification of tumour sizes as shown in (d). Data are mean and s.d. f, Representative bioluminescent images of orthotopically implanted HCT116 tumours expressing Dox-inducible control or POLR2A shRNA following Dox treatment.