“Genes and the Microenviroment: Two Faces of Who We Are” – Mina Bissell
Arizona State University, Arizona State University - Tempe Campus, 727 East Tyler Street, Tempe, AZ 85287
Mina J. Bissell, Ph.D., Distinguished Scientist, Life Sciences Division
Lawrence Berkeley National Laboratory, Berkeley, CA
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The work from Dr. Bissell’s laboratory in the last three decades has led a field that is now central to the current recognition and acceptance of the importance of context/microenvironment and extracellular matrix (ECM) in regulation of gene expression,; and underscored the relationship of the ECM and microenvironment to the plasticity of both the differentiated state and tumors.
Dr. Bissell will discuss how she and her colleagues have developed and use 3-dimensional models of normal mammary gland and mammary tumors from both mice and humans to understand breast cancer. She will present recent work on the seminal role of tissue and organ architecture in cancer research, specifically regulation of tissue specificity and plasticity. Dr. Bissell will also discuss work with newer, more complex models developed to better understand metastasis and dormancy.
She will show a mechanism to underscore the model of dynamic reciprocity and how the ECM and basement membrane signal to the nucleus, via intricate interactions with nuclear actin to provide cell and tissue quiescence; discoveries of unique functions for MMPs (a possible explanation for why anti-MMP therapies failed; and a recent discovery of a novel movement through kinetic imaging of how a unit of tissue function in the mammary gland (an acinus) is formed in the normal breast, lost in malignancy and reformed by controlling the microenvironment and restoring tissue context and architecture. Dr. Bissell will discuss why these concepts and models have profound implications for prognosis, drug resistance and therapy of cancer.
Recent publications from the Bissell laboratory:
Tanner K, Mori H, Mroue R, Bruni-Cardoso A and Bissell MJ (2012) Coherent angular motion in the establishment of multicellular architecture of glandular tissues. Proc Natl Acad Sci U S A. 2012 Jan 25.
Kim J, Villadsen R, Sørlie T, Fogha L, Grønlund SZ, Fridriksdottir AJ, Kuhn I, Rank F, Wieleng VT, Solvang H, Edwards PAW, Børresen-Dale AL, Rønnov-Jessen L, Bissell MJ*, Petersen OW* (2012). Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity. Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6124-9. *Both senior authors contributed equally
Lee SY, Meier R, Furuta S, Lenburg ME, Kenny PC, Xu R and Bissell MJ (2012) Identification and characterization of FAM83A, a clinically-relevant cancer-associated gene which interacts with c-RAF and PI3K, and confers EGFR-TKI resistance in breast cancer cells. Journal Clinical Investigation. 2012 Aug 13. pii: 60498. doi: 10.1172/JCI60498.