Suppression of Apoptosis by Basement Membrane Requires three-dimensional Tissue Organization and Withdrawal from the Cell Cycle

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The basement membrane (BM) extracellular matrix induces differentiation and suppresses apoptosis in mammary epithelial cells, whereas cells lacking BM lose their differentiated phenotype and undergo apoptosis. Addition of purified BM components, which are known to induce {beta}-casein expression, did not prevent apoptosis, indicating that a more complex BM was necessary. A comparison of culture conditions where apoptosis would or would not occur allowed us to relate inhibition of apoptosis to a complete withdrawal from the cell cycle, which was observed only when cells acquired a three-dimensional alveolar structure in response to BM. In the absence of this morphology, both the ... continued below

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Boudreau, N.; Werb, Z. & Bissell, M.J. December 28, 1995.

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The basement membrane (BM) extracellular matrix induces differentiation and suppresses apoptosis in mammary epithelial cells, whereas cells lacking BM lose their differentiated phenotype and undergo apoptosis. Addition of purified BM components, which are known to induce {beta}-casein expression, did not prevent apoptosis, indicating that a more complex BM was necessary. A comparison of culture conditions where apoptosis would or would not occur allowed us to relate inhibition of apoptosis to a complete withdrawal from the cell cycle, which was observed only when cells acquired a three-dimensional alveolar structure in response to BM. In the absence of this morphology, both the G1 cyclin kinase inhibitor p21/WAF-I and positive proliferative signals including c-myc and cyclin Dl were expressed and the retinoblastoma protein (Rb) continued to be hyperphosphorylated. When we overexpressed either c-myc in quiescent cells or p21 when cells were still cycling, apoptosis was induced. In the absence of three-dimensional alveolar structures, mammary epithelial cells secrete a number of factors including transforming growth factor a and tenascin, which when added exogenously to quiescent cells induced expression of c-myc and interleukin-{beta}1-converting enzyme (ICE) mRNA and led to apoptosis. These experiments demonstrate that a correct tissue architecture is crucial for long-range homeostasis, suppression of apoptosis, and maintenance of differentiated phenotype.

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  • Journal Name: Proceedings of the National Academy of Sciences; Journal Volume: 93; Journal Issue: 8; Related Information: Journal Publication Date: Apr. 16, 1996

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  • Report No.: LBL-38481
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 1007187
  • Archival Resource Key: ark:/67531/metadc831882

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  • December 28, 1995

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  • May 19, 2016, 3:16 p.m.

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  • June 16, 2016, 5:08 p.m.

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Boudreau, N.; Werb, Z. & Bissell, M.J. Suppression of Apoptosis by Basement Membrane Requires three-dimensional Tissue Organization and Withdrawal from the Cell Cycle, article, December 28, 1995; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc831882/: accessed September 20, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.