Fig. 4. CTR9 is required for PDAC growth.

a Luciferase imaging of KPC-cell–derived tumors expressing NTC (non-targeting control) shRNA or shRNA against CTR9 upon orthotopic transplantation into C57BL/6 J mice. Doxycycline treatment was started 7 days after transplantation. Luciferase activity is shown at day 7 after transplantation and after 2 or 4 weeks of doxycycline treatment. b Change of tumor size of KPC tumors expressing doxycycline-inducible shNTC (left) or shCTR9 (right) relative to the start of doxycycline treatment on day 7. The plot shows the log₁₀ of the ratio of luciferase activity at the indicated times relative to day 7. Results are presented as mean ± S.E.M. P values were calculated using the unpaired two-sided t-test. n = 6 mice for shNTC+Dox and shCTR9-Dox, while n = 11 mice for shCTR9+Dox. c Kaplan–Meier plot of mice transplanted with KPC cells expressing doxycycline-inducible shCTR9 or shNTC. Doxycycline was added to the food for 12 weeks as indicated. d Immunohistochemistry of pancreatic tumors expressing shRNA against CTR9. Mice were treated for 3 days with or without doxycycline and AZD6738 or vehicle. Sections were stained with anti-pKAP1 and anti-γ-H2AX antibodies. Scale bar: 100 µm. e Percentage of pKAP1 or γ-H2AX positive cells present in the tumor tissue. Positive cells were counted after 3 days of CTR9 depletion and AZD6738 treatment. Results are presented as mean ± S.E.M. Each dot represents an independent tumor and P values were calculated using the unpaired two-sided t-test. n = 3 independent tumors except for pKAP1 staining of AZD6738 treated mice, n = 2. f Kaplan–Meier plot of mice transplanted with KPC cells expressing doxycycline-inducible shCTR9, shMYC or shNTC. Expression of shRNAs was induced with doxycycline from day 7 for 12 weeks in all mice. Mice were treated with AZD6738 or vehicle from day 7 for 7 weeks. Source data are provided as a Source Data file.