When well-characterized ER+ breast cancer cell lines were cultured in stiff ECM in vitro (MCF7 and T47D cells in 3-dimensional collagen cultures and tunable polyacrylamide substrates), PRL was less able to activate JAK2/STAT5, but more strongly activated FAK-SRC-ERK1/2, associated with increased localization of PRLR in focal adhesions (167, 179). This evidence concerns the gene STAT5A and breast cancer.