Figure 5.

Extinction of Pin1 sensitizes BRCA1-WT breast cancer cells to DNA damage. Colony formation assays were performed with shPin1 or control cells treated with IR(A–C) or olaparib (D–F). MCF10A (A), MCF7 (B and E), T47D (C and F), MDA-MB-231 (D). G and H, Effect of combining Pin1 knockdown with olaparib in suppressing the viability of BRCA1-proficient cells. Stable shPin1 or shControl MDA-MB-231 (G) and MCF7 (H) cells were treated with olaparib (10 μmol/L), or transfected with either WT or catalytically inactive Pin1 (S67E). Viability of shPin1 or control cells was examined in response to olaparib or ATRA in MDA-MB-231 (G) or MCF7 (H). I–K, Pin1 depletion sensitizes BRCA1-proficient breast tumors to PARP inhibitor, but not to ATRA treatment. MDA-MB-231 cells with stable expression of shControl, shPin1, or shPin1 plus Pin1 (WT or S67E; 1.5 million/mouse) were implanted into fat pads of nude mice and treatments were started 2 weeks after inoculation. Treatments were continued for 5 weeks when animals were euthanized. Tumor growth curve is shown in I. The harvest tumor was measured (J) and weighted (K). *, P < 0.05; ***, P < 0.001