Abstract
Epithelial cells form tubular and acinar structures notable for a hollow lumen. In three‐dimensional (3D) culture models utilizing MCF10A mammary epithelial cells, hollow acini form due to integrin‐dependent polarization and survival of cells contacting extracellular matrix (ECM), and the apoptosis of inner cells of acini lacking ECM contact. Here, we report that cAMP‐dependent protein kinase A (PKA) promotes hollow acini formation via two mechanisms. First, cAMP accelerates the polarization of outer cells due to ERK/MAPK inhibition. Second, cAMP, promotes the death of inner cells occupying the lumen. In the absence of cAMP, apoptosis is delayed resulting in profound luminal filling. cAMP‐dependent apoptosis is accompanied by a posttrascriptional increase in the proapoptotic protein BIM, which is at least partially ERK‐independent. These data demonstrate that cAMP regulates lumen formation in mammary epithelial cell cultures both through acceleration of polarization of outer cells and apoptosis of inner cells of the acinus.This study was supported by NIH grants to K.E.M (R01 DK074398 and P01 AI53194), S.K. (DK082115), and J.D (RO1 CA126792). P.I.N. was supported by a fellowship from the German Research Society (DFG; Ne‐897/1‐1).
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