Tissue structure, nuclear organization, and gene expression in normal and malignant breast.

摘要: Because every cell within the body has same genetic information, a significant problem in biology is to understand how cells tissue express genes selectively. A sophisticated network of physical and biochemical signals converge highly orchestrated manner bring about exquisite regulation that governs gene expression diverse tissues. Thus, ultimate decision proliferate, tissue-specific genes, or apoptose must be coordinated response its adhesive, growth factor, hormonal milieu. The unifying hypothesis examined this overview unit function higher organisms neither genome nor alone but complex, three-dimensional tissue. This because there are bidirectional connections between components cellular microenvironment (growth factors, hormones, extracellular matrix) nucleus. These made via membrane-bound receptors transmitted nucleus, where result modifications nuclear matrix chromatin structure lead selective expression. need studied "in context", i.e., proper structure, if one pathways connect genome. In last decades, we have used well-characterized human mouse mammary lines "designer microenvironments" create an appropriate context study use culture assay, developed with reconstituted basement membrane, allowed us distinguish normal malignant breast easily rapidly. Whereas become arrested form organized "acini," tumor continue grow, pile up, general fail respond microenvironmental cues. By correcting matrix-receptor (integrin) signaling balance, been able revert phenotype when cultured in, on, membrane. Most recently, shown whereas beta1 integrin epidermal factor receptor signal transduction integrated reciprocally cultures, on plastic (two-dimensional monolayers), these not coordinated. Finally, demonstrated that, rather than passively reflecting changes expression, organization itself can modulate phenotype. We conclude dominant over genome, may new paradigm for epithelial-specific regulated vivo. also argue unless critically altered, malignancy will progress, even presence multiple chromosomal mutations.