Abstract: Series 103, Lecture 5

The Harvey Lectures Series 103 (2007—2008)

previous lecture | next lecture

Lecture #5: Thursday, March 20, 2008 — Time and Location

The Microenvironment / Genome Axis in Tissue Specificity: The Role of Extracellular Matrix and Organ Architecture

Mina J Bissell, PhD

Mina J Bissell, PhD

Distinguished Scientist

Lawrence Berkeley National Laboratory

Berkeley, California

Dr Bissell's Website

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.