Journal
CANCER AND METASTASIS REVIEWS
Volume 28, Issue 1-2, Pages 167-176Publisher
SPRINGER
DOI: 10.1007/s10555-008-9178-z
Keywords
Acinar morphogenesis; Chromatin organization; Cytoskeleton; Extracellular matrix; Mammary-specific function; Microenvironment; Tissue architecture
Categories
Funding
- Office of Biological and Environmental Research of the Department of Energy [DOE-AC03-76SF00098]
- National Institutes of Health [CA112970-01, R01CA057621, R01CA064786]
- Breast Cancer Research Program (BCRP) of the Department of Defense (DOD)
- DOD BCRP [DAMD17-02-1-0441, W81XWH-05-1-0339]
- California BCRP Dissertation Award
- NATIONAL CANCER INSTITUTE [R01CA064786, U54CA112970, R01CA057621] Funding Source: NIH RePORTER
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Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra-to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.
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