Figure 6.
Reprogramming of RB/E2F pathway via CDK4/6 inhibition restricts metastases. A, Western blotting analysis of phospho RB pS780 and lamin B. B, Quantitative cell migration and invasion kinetics in PC3-ML cells treated with DMSO or PD 0332991. C, Schematic representation of experimental design showing experimental metastasis and timing of drug treatments and endpoint analysis. D, Graphic representation of weekly body weights in response to PD 0332991 treatment. E, Representative images with indicated time points (left) and graphic representation of tumor luminescence (right). F, Hematoxylin and eosin (H&E) and pRb IHC staining (×200 and ×400) of lung metastases in response to vehicle or PD 0332991. Arrow, enlarged region. G, Western blotting analysis of phospho RB pS780, E-cadherin, vimentin, and lamin B in PC3-ML–induced lung metastases in response to DMSO or PD 0332991. H, qRT-PCT analysis of RHAMM mRNA from lung tissue and whole blood of PC3-ML tumor–bearing animals treated with DMSO or PD 0332991. Each experimental group used 6 or more animals. Each data point is a mean ± SD from three or more independent experiments. **, P < 0.05 was considered as statistically significant.