Mutant p53 Disrupts Mammary Acinar Morphogenesis via the Mevalonate Pathway

ABSTRACT: p53 is a frequent target for mutation in human tumors and previous studies have revealed that these missense mutant proteins can actively contribute to tumorigenesis. To elucidate how mutant p53 might contribute to mammary carcinogenesis we employed a three-dimensional (3D) culture model. In 3D culture non-malignant breast epithelial cells form structures reminiscent of acinar structures found in vivo, whereas breast cancer cells form highly disorganized and in some cases invasive structures. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the sterol biosynthesis, or mevalonate, pathway as significantly upregulated by a tumor-derived mutant p53. Using statins and st

ORGANISM(S): Homo sapiens

SUBMITTER: William Freed-Pastor 

PROVIDER: E-GEOD-31812 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress