We investigated the effect of this physiologically relevant stiffness range relating to the various MD categories on RASSF1A gene and protein expression in the DCIS.com model of early stage human breast malignancy, using culture on Matrigel (50–150 Pa) and a semi-synthetic extracellular matrix mimic based on photocrosslinkable gelatin (gelatin methacryloyl, or GelMA) (0.5–64 kPa), respectively. Here, RASSF1 is linked to ductal breast carcinoma in situ.