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This study, by Pappas and colleagues (beginning on page 1051), demonstrates that the p53 tumor suppressor maintains baseline expression of numerous other well-validated tumor suppressor genes. Mammary epithelial cells grown in 3D culture form acinar structures that are suitable model systems to study signaling and growth properties. We used CRISPR/Cas9-mediated genetic modifications in the nontumorigenic mammary epithelial cell line MCF10A and found that interruption of the baseline activation of PTEN by p53 increases tumorigenic properties by influencing the size of the acini, proliferation, and signaling in 3D culture. Photographs shown are created by immunofluorescence of the acini structures for various signaling proteins.