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. Author manuscript; available in PMC: 2022 Jul 15.
Published in final edited form as: Cancer Res. 2021 Nov 22;82(2):248–263. doi: 10.1158/0008-5472.CAN-21-1991

Figure 1. Loss of Notch1 or Notch2 Accelerates SCLC Tumorigenesis.

Figure 1.

(A) Schematic of the adenovirus used to infect lox-stop-lox (LSL)-Cas9 mice. RPP = sgRb1, sgTrp53, sgRbl2. sg “T”= sgNotch1, sgNotch2, sgAscl1 or sgControl (nontargeting sgRNA). (B) Immunoblot analysis of MEFs expressing Cas9 infected with the sgControl RPP, sgNotch1 RPP, or sgNotch2 RPP adenoviruses as indicated. (C) Immunoblot analysis of sgControl RPP 631 cells (top) or MEFs expressing Cas9 (bottom) infected with the sgControl RPP and sgAscl1 RPP adenoviruses as indicated. (D) Schematic of the intratracheal injection (IT) approach to deliver adenoviruses to the lungs of mice. (E) Quantification of the percent of mice with lung lesions determined by monthly lung MRIs up until 12 months. For sgNotch2 RPP or sgAscl1 RPP vs. sgControl RPP, p<0.0001; for sgNotch1 RPP vs sgControl RPP p<0.05 determined by Chi-Square Test for Trend. (F) Tumor volume measurements of individual mice determined by lung MRIs at the times indicated (in months) after IT injection of the adenovirus indicated into LSL-Cas9 mice. (G) Median overall survival up until 18 months of LSL-Cas9 mice IT injected with the indicated adenoviruses. p=0.1579 for sgNotch1 RPP vs. sgControl RPP, p=0.1860 for sgNotch2 RPP vs. sgControl RPP, p=0.024 for sgAscl1 RPP vs. sgControl RPP. For E-G, n=10 mice (sgNotch1 RPP), n=10 mice (sgNotch2 RPP), n=7 mice (sgAscl1 RPP) or n=8 mice (sgControl RPP). (H) Representative lung MRIs of mice with lung lesions at the times indicated (in months) after IT injection of the indicated adenoviruses.