Collagen density regulates xenobiotic and hypoxic response of mammary epithelial cells
Collagen density regulates xenobiotic and hypoxic response of mammary epithelial cells
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DOI：
10.1016/j.etap.2014.10.017
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发表时间：
2015-01-01
影响因子：
4.3
通讯作者：
Keely, Patricia J.
中科院分区：
文献类型：
--
作者：
Curran, Colleen S.;Carrillo, Esteban R.;Keely, Patricia J.
Breast density, where collagen I is the dominant component, is a significant breast cancer risk factor. Cell surface integrins interact with collagen, activate focal adhesion kinase (FAK), and downstream cell signals associated with xenobiotics (AhR, ARNT) and hypoxia (HIP-1 alpha, ARNT). We examined if mammary cells cultured in high density (HD) or low density (LD) collagen gels affected xenobiotic or hypoxic responses. ARNT production was significantly reduced by HD culture and in response to a FAK inhibitor. Consistent with a decrease in ARNT, AhR and HIF-1 alpha reporter activation and VEGF production was lower in HD compared to LO. However, P450 production was enhanced in HD and induced by AhR and HIP-1 alpha agonists, possibly in response to increased NF-kappa B activaton. Thus, collagen density differentially regulates downstream cell signals of AhR and HIP-1 alpha by modulating the activity of FAK, the release of NF-kappa B transcriptional factors, and the levels of ARNT. (C) 2014 Elsevier B.V. All rights reserved.
