@article {531,
	title = {beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium.},
	journal = {Cancer Cell},
	volume = {2},
	year = {2002},
	month = {2002 Sep},
	pages = {205-16},
	abstract = {<p>Tumor cells can evade chemotherapy by acquiring resistance to apoptosis. We investigated the molecular mechanism whereby malignant and nonmalignant mammary epithelial cells become insensitive to apoptosis. We show that regardless of growth status, formation of polarized, three-dimensional structures driven by basement membrane confers protection to apoptosis in both nonmalignant and malignant mammary epithelial cells. By contrast, irrespective of their malignant status, nonpolarized structures are sensitive to induction of apoptosis. Resistance to apoptosis requires ligation of beta4 integrins, which regulates tissue polarity, hemidesmosome formation, and NFkappaB activation. Expression of beta4 integrin that lacks the hemidesmosome targeting domain interferes with tissue polarity and NFkappaB activation and permits apoptosis. These results indicate that integrin-induced polarity may drive tumor cell resistance to apoptosis-inducing agents via effects on NFkappaB.</p>
},
	keywords = {Apoptosis, Basement Membrane, Breast Neoplasms, Cell Polarity, Epithelial Cells, Extracellular Matrix, Female, Gene Expression Regulation, Neoplastic, Humans, Integrin beta4, NF-kappa B, Tumor Cells, Cultured},
	issn = {1535-6108},
	author = {Weaver, Valerie M and Leli{\`e}vre, Sophie and Lakins, Johnathon N and Chrenek, Micah A and Jones, Jonathan C R and Giancotti, Filippo and Werb, Zena and Bissell, Mina J}
}
@article {526,
	title = {The organizing principle: microenvironmental influences in the normal and malignant breast.},
	journal = {Differentiation},
	volume = {70},
	year = {2002},
	month = {2002 Dec},
	pages = {537-46},
	abstract = {<p>The current paradigm for cancer initiation and progression rests on the groundbreaking discoveries of oncogenes and tumor suppressor genes. This framework has revealed much about the role of genetic alterations in the underlying signaling pathways central to normal cellular function and to tumor progression. However, it is clear that single gene theories or even sequential acquisition of mutations underestimate the nature of the genetic and epigenetic changes in tumors, and do not account for the observation that many cancer susceptibility genes (e.g. BRCA1, APC) show a high degree of tissue specificity in their association with neoplastic transformation. Therefore, the cellular and tissue context itself must confer additional and crucial information necessary for mutated genes to exert their influence. A considerable body of evidence now shows that cell-cell and cell-extracellular matrix (ECM) interactions are essential organizing principles that help define the nature of the tissue context, and play a crucial role in regulating homeostasis and tissue specificity. How this context determines functional integrity, and how its loss can lead to malignancy, appears to have much to do with tissue structure and polarity.</p>
},
	keywords = {Apoptosis, Breast, Breast Neoplasms, Coculture Techniques, Female, Humans, Signal Transduction},
	issn = {0301-4681},
	doi = {10.1046/j.1432-0436.2002.700907.x},
	author = {Bissell, Mina J and Radisky, Derek C and Rizki, Aylin and Weaver, Valerie M and Petersen, Ole W}
}
