Remodeling and increased stiffness of the extracellular matrix is a hallmark of solid cancers and contributes to tumor progression through increased proliferation, survival and migration. Mechanotransduction, the process in which cells sense and transduce mechanical signals, can result in transcriptional changes that in turn alter cellular behavior. In vitro culturing of MCF10ACA1a (CA1a) breast cancer cells on polyacrylamide-based hydrogels of variable stiffness revealed drastic changes in morphology, indicating a stiffness dependent induction of a malignant phenotype. We used two different techniques, DNA microarray and RNA sequencing, to characterize the transcriptome of CA1a cells on low (500 Pa) and high (8000 Pa) stiffness, corresponding to the stiffness of normal breast and breast cancer, respectively. Overall design: 3 biological replicates of MCF10CA1a cells cultured on low (500 pa) or high (8000 pa) stiffness.