β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium Journal Article
| Authors: | Weaver, V. M.; Lelièvre, S.; Lakins, J. N.; Chrenek, M. A.; Jones, J. C. R.; Giancotti, F.; Werb, Z.; Bissell, M. J. |
| Article Title: | β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium |
| Abstract: | 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 β4 integrins, which regulates tissue polarity, hemidesmosome formation, and NFκB activation. Expression of β4 integrin that lacks the hemidesmosome targeting domain interferes with tissue polarity and NFκB activation and permits apoptosis. These results indicate that integrin-induced polarity may drive tumor cell resistance to apoptosis-inducing agents via effects on NFκB. Copyright © 2002 Cell Press. |
| Keywords: | controlled study; protein expression; human cell; cancer growth; protein domain; cytology; metabolism; apoptosis; basement membrane; immunoglobulin enhancer binding protein; pathology; tumor cells, cultured; breast neoplasms; physiology; cancer resistance; extracellular matrix; gene expression regulation; gene expression regulation, neoplastic; cell culture; three dimensional imaging; breast tumor; breast carcinoma; nf-kappa b; epithelium cell; epithelial cells; cell polarity; protein structure; cell protection; ultrastructure; breast cell; growth rate; beta4 integrin; integrin beta4; protein synthesis regulation; cell ultrastructure; hemidesmosome; humans; human; female; priority journal; article |
| Journal Title: | Cancer Cell |
| Volume: | 2 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2002-09-01 |
| Start Page: | 205 |
| End Page: | 216 |
| Language: | English |
| DOI: | 10.1016/s1535-6108(02)00125-3 |
| PUBMED: | 12242153 |
| PROVIDER: | scopus |
| PMCID: | PMC2788997 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
