Bissell, M

Beliveau, A
Schwarz ,R

Alcaraz, J
Ao, M
Berruyer-Pouyet, C
Kenny, P
LaBarge, M
Mori, H
Nelson, C
Rizki, A
Spencer, V
Veiseh, M
Weigelt, B
Xu, R

Bascom, J
Chen, C
Inman, J
Lee, E
Lee, G
Levy, D
Zhang, H

Boudreau, A
Moonlee, S-Y
Mroue, R

Vann, K

Andersen, K
Lelievre, S
Liu, H
Martin, S
Muschler, J
Myers, C
Park, C
Peterson, O
Radisky, D
Turley, E

Thorne, D

Williams, N


Microenvironmental influences on gene expression and tissue specificity in normal and malignant breast.

The laboratory is interested in the role of extracellular matrix (ECM), its receptors and its degrading enzymes as central modulators of tissue-specific gene expression, signal transduction, apoptosis and cancer. We use the mammary gland of mice and humans to study the above processes in breast and breast cancer.

Given that all tissues share the same DNA sequences, the question of how tissue specificity is maintained and how it goes awry in cancer is a central problem in biology. Our laboratory has developed "designer microenvironments" in three-dimensional (3D) cultures to study the role of the microenvironment and tissue architecture in normal and malignant cells and how these external factors shape signal transduction in tissues. We show that non-malignant and malignant mammary cells isolated from either human or mouse can be distinguished rapidly and unequivocally in our 3D assays. We can revert the malignant phenotype if the structure is restored in 3D. We also show that while all signal transduction pathways are integrated reciprocally in 3D, these pathways appear to be disconnected on tissue culture plastic (2D). Finally, we show that aberration in microenvironmental control or loss of ECM can lead to genomic instability. We conclude that the structure of the tissue is dominant over the genome and that we may need a new paradigm for how tissue-specific genes are regulated in vivo.

The laboratory is also engaged in the studies of branching morphogenesis in the mammary gland, with specific emphasis on the role of ECM, its degrading enzymes (MMPs) and the morphogen, epimorphin (syntaxin 2). Finally, we are also developing theoretical models of signal transduction in 3D tissues. The laboratory comprises a multidisciplinary group of scientists, postdoctoral fellows and graduate students (biologists, bioinformaticists, bioengineers, physicists). We collaborate closely with the laboratories of Professors Ole W. Petersen (The Panum Institute, University of Copenhagen, Denmark) and Zena Werb (Department of Anatomy, University of California, San Francisco) as well as a number of other investigators here at LBNL and on the University of California, Berkeley campus. Please see the selected literature and also visit:

Mina J. Bissell
Distinguished Scientist/
Life Sciences Division

One Cyclotron Rd.
Mailstop: 977R225A
Berkeley, CA 94720
tel: (510)486-4368
fax: (510)486-5586
website: Bissell Lab



Bissell Laboratory Website

Complete Publications List (pdf)

Selected Significant Publications (out of 277):

13. Bissell MJ, Rambeck WA, White RC, Bassham JA. (1976). Glycerol phosphate shuttle in virus-transformed cells in culture. Science 191:856-858.

38. Parry G, Bartholomew JC, Bissell MJ. (1980). Role of src gene in growth regulation of Rous sarcoma virus-infected chicken embryo fibroblasts. Nature 288:720-722.

46. Bissell MJ, Hall HG and Parry G. (1982) How does extracellular matrix direct gene expression? J Theor Biol 99:31-68.

52. Dolberg DS and Bissell MJ. (1984) Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309:552-556.

55. Dolberg DS, Hollingsworth R, Hertle M and Bissell MJ. (1985) Wounding and its role in RSV-induced tumor formation. Science 230:676-678.

91. Martins-Green M and Bissell MJ. (1990) Localization of 9E3/CEF-4 in avian tissues: expression is absent in Rous sarcoma virus-induced tumors but is stimulated by injury. J Cell Biol 110(3):581-595.

93. Sieweke MH, Thompson NL, Sporn MB and Bissell MJ. (1990) Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-▀. Science 248:1656-1660.

102. Streuli CH, Bailey N and Bissell MJ. (1991) Control of mammary epithelial differentiation: Basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol. 115:1383-95. [Selected as one of the 40 Landmark Papers In Cell Biology (Joseph G. Gall and J. Richard McIntosh, eds.). pp. 336-348 (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY].

110. Petersen OW, R°nnov-Jessen L, Howlett AR and Bissell MJ. (1992) Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci USA 89:9064-9068.

111. Schmidhauser C, Casperon GF, Myers CA, Sanzo KT, Bolten S and Bissell MJ. (1992) A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of ▀-casein gene expression. Mol Cell Biol 3(6):699-709.

132. Boudreau N, Sympson CJ, Werb Z and Bissell MJ. (1995) Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267:891-893.

166. Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C and Bissell MJ. (1997) Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo using integrin blocking antibodies. J Cell Biol 137:231-246.

176. Myers CA, Schmidhauser C, Mellentin-Michelotti J, Fragoso G, Roskelley CD, Casperson G, Mossi R, Pujuguet P, Hager G and Bissell MJ. (1998) Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation. Mol Cell Biol 18(4):2184-2195.

192. Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier JP, Gray JW, Pinkel D, Bissell MJ and Werb Z. (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98(2):137-46.

212. Gudjonsson T, Villadsen R, Nielsen HL, R°nnov-Jensen L, Bissell MJ, and Petersen OW. (2002) Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes & Development 16(6):693-706.

215. Weaver VM, LeliŔvre SA, Lakins JN, Chrenek MA, Jones JCR, Giancotti F, Werb Z and Bissell MJ. (2002) 4 Integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2:205-216.

249. Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z and Bissell MJ (2005). Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436(7047):123-7.

258. Park CC, Zhang H, Pallavicini M, Gray JW, Baehner F, Park CJ, Bissell MJ (2006). ▀1 Integrin Inhibitory Antibody Induces Apoptosis of Breast Cancer Cells, Inhibits Growth, and Distinguishes Malignant from Normal Phenotype in Three Dimensional Cultures and In vivo. Cancer Research Feb 1;66(3):1526-35.

265. Fournier MV, Martin KJ, Kenny PA, Xhaja K, Bosch I, Yaswen P and Bissell, MJ (2006). Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Research. 2006 Jul 15;66(14):7095-102.

268. Nelson, CM, van Duijn M, Inman JL, Fletcher DA and Bissell MJ(2006). Tissue Geometry Determines Sites of Branching Morphogenesis in Organotypic Cultures. Science Oct 13;314(5797):298-300.

271. Kenny PA, Bissell MJ (2007). Targeting TACE-Dependent EGFR-ligand Shedding in Breast Cancer. Journal of Clinical Investigation. Clin. Invest., Jan 2007; doi:10.1172/JCI29518.

Last updated: 4/25/07