Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling

Janice Murtagh, Emmett McArdle, Emer Gilligan, Laura Thornton, Fiona Furlong, Finian Martin

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Mammary epithelial cells cultured on a concentrated laminin-rich extracellular matrix formed 3D acinar structures that matured to polarized monolayers surrounding a lumen. In the absence of glucocorticoids mature acinus formation failed and the expression of an acinus-associated, activator protein 1 (AP1) and nuclear factor kappaB transcription factor DNA-binding profile was lost. Treatment with the JNK inhibitor, SP600125, caused similar effects, whereas normal organization of the mammary epithelial cells as acini caused JNK activation in a glucocorticoid-dependent manner. The forming acini expressed BRCA1, GADD45beta, MEKK4, and the JNK activating complex GADD 45beta-MEKK4 in a glucocorticoid-dependent fashion. JNK catalyzed phosphorylation of c-Jun was also detected in the acini. In addition, expression of beta4 integrin and in situ occupation of its promoter by AP1 components, c-Jun and Fos, was glucocorticoid dependent. These results suggest that glucocortocoid signaling regulates acinar integrity through a pathway involving JNK regulation of AP1 transcription factors and beta4 integrin expression.
Original languageEnglish
Pages (from-to)133-43
Number of pages11
JournalThe Journal of cell biology
Volume166
Issue number1
DOIs
Publication statusPublished - 05 Jul 2004

ASJC Scopus subject areas

  • Cell Biology

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