Cell Growth & Differentiation, Vol 8, Issue 2 251-260, Copyright © 1997 by American Association of Cancer Research

ARTICLES

Apoptosis is accompanied by changes in Bcl-2 and Bax expression, induced by loss of attachment, and inhibited by specific extracellular matrix proteins in mammary epithelial cells

GR Merio, N Cella and NE Hynes
Friedrich Miescher Institute, Basel, Switzerland.

Mammary epithelial cells (MEC) undergo programmed cell death (PCD) when deprived of serum and growth factors at high cell density but not at low density. The addition of epidermal growth factor and insulin to serum-free medium (SFM) completely restores cell survival. In this report, we examine the role of cell-cell and cell-matrix interaction. When cell attachment is prevented, PCD is markedly accelerated. This effect is observed in cells collected at low or high density and is unaffected by calcium depletion. Cells plated in SFM on purified laminin, tenascin C, or collagen IV-coated dishes, as well as on dishes coated with endogenous extracellular matrix deposited by HC11 mammary cells, show reduced PCD. The addition of soluble laminin or tenascin C to suspension cultures of MECs also partially inhibits PCD. In contrast, no effect is seen with fibronectin or collagen I. These results indicate that reduced contact with a solid substrate contributes to the induction of PCD, which might partially explain the fact that it is only observed in confluent cultures. Ectopic Bcl-2 expression in MCF-10-A and HC11 mammary cells results in a complete suppression of PCD. In MCF-10-A cells, the level of endogenous Bcl-2 increases when the survival factors epidermal growth factor and insulin are added to the SFM but is unaffected by cell density. On the contrary, Bax protein expression increases sharply with cell density but does not change upon addition of epidermal growth factor and insulin. When compared to lactating tissue, Bcl-2 protein levels decrease during mammary gland involution. Bax protein levels increase during lactation and remain high during involution. These data suggest that Bcl-2 and Bax might be intracellular mediators of signals that influence MEC apoptosis.

This article has been cited by other articles:

				G. F. Weber and A. S. Menko The Canonical Intrinsic Mitochondrial Death Pathway Has a Non-apoptotic Role in Signaling Lens Cell Differentiation J. Biol. Chem., June 10, 2005; 280(23): 22135 - 22145. [Abstract] [Full Text] [PDF]

				K. Imai, B. A. Mercer, L. L. Schulman, J. R. Sonett, and J. M. D'Armiento Correlation of lung surface area to apoptosis and proliferation in human emphysema Eur. Respir. J., February 1, 2005; 25(2): 250 - 258. [Abstract] [Full Text] [PDF]

				J. R. Beckley, B. U. Pauli, and R. C. Elble Re-expression of Detachment-inducible Chloride Channel mCLCA5 Suppresses Growth of Metastatic Breast Cancer Cells J. Biol. Chem., October 1, 2004; 279(40): 41634 - 41641. [Abstract] [Full Text] [PDF]

				R. Castellon, S. Caballero, H. K. Hamdi, S. R. Atilano, A. M. Aoki, R. W. Tarnuzzer, M. C. Kenney, M. B. Grant, and A. V. Ljubimov Effects of Tenascin-C on Normal and Diabetic Retinal Endothelial Cells in Culture Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2758 - 2766. [Abstract] [Full Text] [PDF]

				K. T. Iida, H. Suzuki, H. Sone, H. Shimano, H. Toyoshima, S. Yatoh, T. Asano, Y. Okuda, and N. Yamada Insulin Inhibits Apoptosis of Macrophage Cell Line, THP-1 Cells, via Phosphatidylinositol-3-Kinase-Dependent Pathway Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 380 - 386. [Abstract] [Full Text] [PDF]

				W. Wick, C. Grimmel, C. Wild-Bode, M. Platten, M. Arpin, and M. Weller Ezrin-Dependent Promotion of Glioma Cell Clonogenicity, Motility, and Invasion Mediated by BCL-2 and Transforming Growth Factor-{beta}2 J. Neurosci., May 15, 2001; 21(10): 3360 - 3368. [Abstract] [Full Text] [PDF]

				S. W. Tobin, M. K. Brown, K. Douville, D. C. Payne, A. Eastman, and B. A. Arrick Inhibition of Transforming Growth Factor {beta} Signaling in MCF-7 Cells Results in Resistance to Tumor Necrosis Factor {{alpha}}: A Role for Bcl-2 Cell Growth Differ., February 1, 2001; 12(2): 109 - 117. [Abstract] [Full Text]

				C. Ip, M. M. Ip, T. Loftus, S. Shoemaker, and W. Shea-Eaton Induction of Apoptosis by Conjugated Linoleic Acid in Cultured Mammary Tumor Cells and Premalignant Lesions of the Rat Mammary Gland Cancer Epidemiol. Biomarkers Prev., July 1, 2000; 9(7): 689 - 696. [Abstract] [Full Text]

				S. Hakimelahi, H. R. Parker, A. J. Gilchrist, M. Barry, Z. Li, R. C. Bleackley, and M. Pasdar Plakoglobin Regulates the Expression of the Anti-apoptotic Protein BCL-2 J. Biol. Chem., April 6, 2000; 275(15): 10905 - 10911. [Abstract] [Full Text] [PDF]

				T. J. Moran, S. Gray, C. A. Mikosz, and S. D. Conzen The Glucocorticoid Receptor Mediates a Survival Signal in Human Mammary Epithelial Cells Cancer Res., February 1, 2000; 60(4): 867 - 872. [Abstract] [Full Text]

				P Schedin, R Strange, T Mitrenga, P Wolfe, and M Kaeck Fibronectin fragments induce MMP activity in mouse mammary epithelial cells: evidence for a role in mammary tissue remodeling J. Cell Sci., January 3, 2000; 113(5): 795 - 806. [Abstract] [PDF]

				S. Buckley, B. Driscoll, L. Barsky, K. Weinberg, K. Anderson, and D. Warburton ERK activation protects against DNA damage and apoptosis in hyperoxic rat AEC2 Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L159 - L166. [Abstract] [Full Text] [PDF]

				A. Brun, F. Rodriguez, J. M. Escribano, and C. Alonso Functionality and Cell Anchorage Dependence of the African Swine Fever Virus Gene A179L, a Viral bcl-2 Homolog, in Insect Cells J. Virol., December 1, 1998; 72(12): 10227 - 10233. [Abstract] [Full Text] [PDF]

				R. C. Elble and B. U. Pauli Tumor Suppression by a Proapoptotic Calcium-activated Chloride Channel in Mammary Epithelium J. Biol. Chem., October 26, 2001; 276(44): 40510 - 40517. [Abstract] [Full Text] [PDF]