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The Microenvironment/Genome Axis in Tissue Specificity:
The Role of Extracellular Matrix and Organ Architecture |
Mina J Bissell, PhD |
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Distinguished Scientist
Lawrence Berkeley National Laboratory
Berkeley, California |
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How tissue specificity is maintained and why it is essentially
lost in cancer are outstanding questions in biology.
In the mammary gland, it is clear that both the architecture
of the gland and its ability to synthesize and transport
milk proteins are dependent on tissue polarity and maintenance
of an intact and functional basement membrane.
We have developed robust 3-D assays that mimic the
morphology and function of the epithelial cells within
the gland. We show that laminin 111 signals via α1 integrin
to alter polarity, cytostructure and chromatin structure
and the status of STAT5 phosphorylation and other
transcription factors to allow milk production.
In malignant cells we show that restoring unit breast
structure (the acinus) by reducing signaling through α1
integrin restores “normal” phenotype in 3-D cultures
reversibly and prevents tumor formation. New model
systems using branching morphogenesis in normal gland
clarify the supreme importance of tissue architecture in
morphogenesis and are shedding light on how cancer
cells could usurp the normal pathways to invade and
metastasize.
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