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First published online October 27, 2005

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Breast cancer: the matrix released

Early on during the development of breast cancer, interactions between epithelial cells and the extracellular matrix (ECM) that regulate normal growth and apoptosis are lost. Laminin 5, a matrix glycoprotein that promotes mammary gland homeostasis, is dysregulated during cancer progression but how this occurs is unclear. Victoria Seewaldt and co-workers now implicate the transcription factor CREB-binding protein (CBP) in the process, showing that it regulates apoptosis and growth of certain mammary epithelial cells by controlling expression of the laminin-5 3 chain (see p. 5005). Basal-type epithelial breast cancers express stratified epithelial cytokeratins and occur in young African-American women and women carrying BRCA1 mutations. The authors show that loss or suppression of CBP expression in basal cytokeratin-positive human mammary epithelial cells results in loss of ECM-mediated growth regulation and apoptosis in vitro. These changes can be reversed by expression of exogenous CBP, as can the inhibition of LAMA3A promoter activity and laminin-5 3-chain expression that accompanies suppression of CBP. The authors suggest that reduced CBP expression in these cells promotes a cellular environment that favours invasive basal-type breast cancer development by reducing ECM-mediated growth control and apoptosis.

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CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5

Eric C. Dietze, Michelle L. Bowie, Krzysztof Mrózek, L. Elizabeth Caldwell, Cassandra Neal, Robin J. Marjoram, Michelle M. Troch, Gregory R. Bean, Kazunari K. Yokoyama, Catherine A. Ibarra, and Victoria L. Seewaldt
JCS 2005 118: 5005-5022. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?