Sci. Signal., 24 May 2011
Illuminating Lumen FormationThe normal architecture of the mammary gland, which contains ductal and acinar structures in which polarized epithelial cells surround a hollow lumen, is disrupted in early neoplastic lesions, such as ductal carcinoma in situ (DCIS). Loss of signaling through the protein kinase p38 can promote breast cancer progression, but exactly where and how p38 inhibits tumor formation has been unclear. Wen et al. used three-dimensional cultures of mammary epithelial cells to explore the role of p38 in lumen formation, which depends on the death of cells that have become detached from the basement membrane, and found that it depended on opposing signals mediated by p38 and extracellular signal–regulated kinase. Cell detachment stimulated p38 signaling, leading to an increase in the abundance of the death-promoting protein BimEL and, thereby, luminal cell death. Moreover, p38 inhibition accelerated the development of DCIS-like lesions in a mouse model of breast cancer. The authors thus conclude that p38 is crucial to lumen formation during mammary gland development and may act at this stage to inhibit tumorigenesis.
Citation: H.-C. Wen, A. Avivar-Valderas, M. S. Sosa, N. Girnius, E. F. Farias, R. J. Davis, J. A. Aguirre-Ghiso, p38α Signaling Induces Anoikis and Lumen Formation During Mammary Morphogenesis. Sci. Signal. 4, ra34 (2011).
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