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. Author manuscript; available in PMC: 2016 Jun 16.
Published in final edited form as: Sci Transl Med. 2015 Dec 16;7(318):318ra202. doi: 10.1126/scitranslmed.aac8773

Fig. 3. Silencing or inhibition of CK1δ provokes breast tumor regression and blocks growth of PDX breast models.

Fig. 3

(A) Left, qPCR data confirming efficient knockdown of CK1δ, but not CK1ε after 72 hours of treatment of MDA-MB-231 shCK1δ-expressing cells with Dox (0.3 μg/ml) (n=3; ***, p=0.0003). Right, corresponding CK1δ protein expression. (B) Cells expressing Dox-inducible CK1δ or non-targeting (NT) shRNA were treated with 1 μg/ml Dox for 72 hours and transfected with vectors expressing CK1δ or GFP cDNA resistant to shRNA. After a further 72 hours, percent cell death was measured by trypan blue dye exclusion in MDA-MB-231-shCK1δ (black) and cells expressing non-targeting shRNAs (NT, white) (n=4; ***, p=0.0001). (C) Growth of orthotopic MDA-MB-231-shCK1δ tumors in mice +/− Dox (administered ad lib in chow, 200 mg/kg), as monitored by caliper measurements (n=8 for each cohort; **, p=0.006). Arrow indicates addition of Dox. (D) CK1δ knockdown in tumor tissue isolated from three independent mice, 7 days after Dox administration began. (E) Immunoblot comparing CK1δ expression in extracts of normal human breast or three independent BMC-4013 PDX tumors. (F) Growth curves of BCM-4013 PDX tumors in mice treated with vehicle (black line) or SR-3029 (blue line). Arrow indicates timing of first dose (n=12 for each cohort; ***, p=0.0002). (G) Kaplan-Meier survival curve corresponding to studies shown in (F) (p value calculated using log-rank test). (H) TUNEL staining on serial sections of vehicle and SR-3029 treated BMC-4013 tumors (representative images are shown) (scale bar=200 μm).