Mammary gland epithelial cells form polarized acinar structures when cultured in 3D matrigel. Treatment with prolactin can activate JAK2-STAT5 pathway. Without laminin-111, STAT5 only shows a transient phosphorylation, which is not suffcient for chromatin remodeling and milk gene expression. After laminin-111 binds integrins and dystroglycan, PI3K re-localize to the basal surface. Rac1 is a downsteam target of PI3K and required for sustained activation of STAT5. Prolactin, together with laminin-111, induces histone acetylation, binding of the SWI/SNF and transcription factors to the promoter and initiates transcription of casein.