BMPR2 mediates BMP7-induced reversible senescence. (A) The expression of BMPR2 and β-tubulin in PC3 mm that had either scrambled shRNA (scramble) or shRNA for BMPR2 (shBMPR2) was examined by Western blot (top) and qRT-PCR (bottom; n = 3). (B) Kaplan-Meier analysis for bone metastasis–free survival of mice after intracardiac injection of PC3 mm cells that carried either scrambled shRNA (scramble; n = 9) or shRNA for BMPR2 (shBMPR2; n = 10) followed by treatment with vehicle or BMP7. Scramble versus Scramble + BMP7: ***, P < 0.0001; shBMPR2 versus shBMPR2 + BMP7: NS; Scramble + BMP7 versus shBMPR2 + BMP7: ***, P = 0.0002 by Log-rank test. (C) PC3 mm/scramble cells and PC3 mm/shBMPR2 cells were treated with or without BMP7, and the expression of p-p38, p38, p21, NDRG1, and β-tubulin was examined by Western blot. (D) The PC3 mm cells stably expressing Tet-shBMPR2 were cultured with (+) or without (−) induction of shBMPR2 in the presence or absence of BMP7, followed by assaying SA–β-gal. −/−, no induction; +/+, continuous induction; +/−, 48-h induction followed by 48-h withdrawal of tetracycline (n = 3). ***, P < 0.001. The expression of BMPR2 and β-tubulin was examined by Western blot (inset). Experiments in A, C, and D were performed three times, the experiment in B was performed twice independently, and representative data are shown. Results are shown as mean ± SEM.