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Involvement of Cathepsin D in Apoptosis of Mammary Epithelial Cells

  • Seol, M.B. ;
  • Bong, J.J. ;
  • Baik, M.
  • Received : 2006.01.17
  • Accepted : 2006.03.30
  • Published : 2006.08.01

Abstract

During involution of the mammary gland after the lactation period, the gland undergoes an extensive epithelial cell death. In our previous study, overexpression of an extracellular proteinase inhibitor (Expi) gene accelerated apoptosis of mammary epithelial cells. Here we found that expression of the cathepsin D gene was induced in the Expi-overexpressed apoptotic cells. To understand the role of cathepsin D in apoptosis, we transfected cathepsin D gene into mammary epithelial HC11 cells and established the stable cell lines overexpressing the cathepsin D gene. We found that overexpression of the cathepsin D gene partially induced apoptosis of mammary epithelial cells. Expression patterns of the cathepsin D gene were examined in mouse mammary gland at various reproductive stages. Expression of the cathepsin D gene was increased during involution stages compared to lactation stages, and highest expression levels were shown at involution on day 4. We also examined expression of the cathepsin D gene in various mouse tissues. Mammary gland at involution on day 2 showed highest levels of cathepsin D mRNA of the mouse tissues that we examined. Liver tissues showed high levels of cathepsin D expression. These results demonstrate that cathepsin D may contribute to the apoptotic process of mammary epithelial cells.

Keywords

Cathepsin D;Apoptosis;Mammary Epithelial Cells

References

  1. Ball, R. K., R. R. Friis, C.-A. Schonenberger, W. Doppler and B. Groner. 1994. Prolactin regulation of $\beta$-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J. 7:2089-2095
  2. Dear, T. N., I. A. Ramshaw and R. F. Kefford. 1988. Differential expression of a novel gene, WDNM1, in nonmetastatic rat mammary adenocarcinoma cells. Cancer Res. 48:5203-5209
  3. Dear, T. N., D. A. McDonald and R. F. Kefford. 1989. Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells. Cancer Res. 49:5323-5328
  4. Feng, Z., A. Marti, B. Jehn, H. J. Altermatt, G. Chicaiza and R. Jaggi. 1995. Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland. J. Cell Biol. 131:1095-1103 https://doi.org/10.1083/jcb.131.4.1095
  5. Marti, A., Z. Feng, H. J. Altermatt and R. Jaggi. 1997. Milk accumulation triggers apoptosis of mammary epithelial cells. Eur. J. Cell. Biol. 73:158-165
  6. Rochefort, H., E. Liaudet and M. Garcia. 1996. Alterations and role of human cathepsin D in cancer metastasis. Enzyme Protein 49:106-116 https://doi.org/10.1159/000468620
  7. Strange, R., F. Li, S. Saurer, A. Burkhardt and R. R. Friis. 1992. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development 115:49-58
  8. Tsukuba, T., K. Okamoto, Y. Yasuda, W. Morikawa, H. Nakanishi and K. Yamamoto. 2000. New functional aspects of cathepsin D and cathepsin E. Mol. Cells. 10:601-611 https://doi.org/10.1007/s100590000019
  9. Uchiyama, Y., S. Waguri, N. Sato, T. Watanabe, K. Ishido and E. Kominami. 1994. Cell and tissue distribution of lysosomal cysteine proteinases, cathepsin B, H, and L, their biological roles. Acta Histochem. Cytochem. 27:287-308 https://doi.org/10.1267/ahc.27.287
  10. Walker, N. I., R. E. Bennett and J. F. R. Kerr. 1989. Cell death by apoptosis during involution of the lactating breast in mice and rats. Am. J. Anatomy 185:19-32 https://doi.org/10.1002/aja.1001850104
  11. Zhivotovsky, B., D. H. Burgess, D. M. Vanags and S. Orrenius. 1997. Involvement of cellular proteolytic machinery in apoptosis. Biochem. Biophys. Res. Commun. 230:481-488 https://doi.org/10.1006/bbrc.1996.6016
  12. Mathiasen, I. S. and M. Jaattela. 2002. Triggering caspaseindependent cell death to combat cancer. Trends in Molecular Medicine 8:212-220 https://doi.org/10.1016/S1471-4914(02)02328-6
  13. Boudreau, N., C. J. Sympson, Z. Werb and M. J. Bissell. 1995. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Sci. 267:891-893 https://doi.org/10.1126/science.7531366
  14. Han, S. E., H. G. Lee, C. H. Yun, Z. S. Hong, S. H. Kim, S. K. Kang, S. H. Kim, J. S. Cho, S. H. Ha and Y. J. Choi. 2005. Effect of cellular zinc on the regulation of C2-ceramide induced apoptosis in mammary epithelial and macrophage cell lines. Asian-Aust. J. Anim. Sci. 18:1741-1745 https://doi.org/10.5713/ajas.2005.1741
  15. Lee, M. J., O. Han, K. Back, Y. J. Choi and M. G. Baik. 2001. Induction of lysozyme gene expression during involution of mouse mammary gland. Asian-Aust. J. Anim. Sci. 14:462-466 https://doi.org/10.5713/ajas.2001.462
  16. Talhouk, R. S., M. J. Bissell and Z. Werb. 1992. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J. Cell Biol. 118:1271-1282 https://doi.org/10.1083/jcb.118.5.1271
  17. Yamamoto, K. 1995. Cathepsin E and cathepsin D: Biosynthesis, processing and subcellular location. In: Takahashi K, editor. Aspartic proteinases: Structure, function, biology and biomedical implications. New York: Plenum Press, 223-229
  18. Bong, J. J., H. H. Kim, O. Han, K. Back and M. Baik. 2004. 24p3 gene is induced during involution of mammary gland and induces apoptosis of mammary epithelial cells. Mol. Cells 17:29-34
  19. Li, M., X. Liu, G. Robinson, U. Bar-Peled, K. U. Wagner, W. S. Young, L. Hennighausen and P. A. Furth. 1997. Mammaryderived signals activated programmed cell death during the first stage of mammary gland involution. Proc. Natl. Acad. Sci. 94:3425-3430
  20. Lowe, S. W., H. E. Ruley, T. Jacks and D. E. Housman. 1993. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957-967 https://doi.org/10.1016/0092-8674(93)90719-7
  21. Lund, L. R., J. Romer, N. Thomasset, H. Solberg, C. Pyke, M. J. Bissell, K. Dano and Z. Werb. 1996. Two distinct phases of apoptosis in mammary gland involution: proteinaseindependent and dependent pathways. Development 122:181-193
  22. Kagedal, K., U. Johansson and K. Ollinger. 2001. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J. 15:1592-1594 https://doi.org/10.1096/fj.00-0708fje
  23. Heinrich, M., J. Neumeyer, M. Jakob, C. Hallas, V. Tchikov, S. Winoto-Morbach, M. Wickel, W. Schneider-Brachert, A. Trauzold, A. Hethke and S. Schutze. 2004. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ. 11:550-563 https://doi.org/10.1038/sj.cdd.4401382
  24. Bidere, N., H. K. Lorenzo, S. Carmona, M. Laforge, F. Harper, C. Dumont and A. Senik. 2003. Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J. Biol. Chem. 278:31401-31411 https://doi.org/10.1074/jbc.M301911200
  25. Roberg, K. 2001. Relocalization of Cathepsin D and Cytochrome c Early in Apoptosis Revealed by Immunoelectron Microscopy. Lab. Invest. 81:149 https://doi.org/10.1038/labinvest.3780222
  26. Marti, A., H. Lazar, P. Ritter and R. Jaggi. 1999. Transcription factor activities and gene expression during mouse mammary gland involution. J. Mammary Gland Biol. Neoplasia 4:145-152 https://doi.org/10.1023/A:1018721107061
  27. Deiss, L. P., H. Galinka, H. Berissi, O. Cohen and A. Kimchi. 1996. Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. EMBO J. 15:3861-3870
  28. Johansson, A. C., H. Steen, K. Ollinger and K. Roberg. 2003. Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine. Cell Death Differ. 10:1253-1259 https://doi.org/10.1038/sj.cdd.4401290
  29. Chomozenski, P. and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156-159
  30. Jung, D. J., J. J. Bong and M. Baik. 2004. Extracellular proteinase inhibitor-accelerated apoptosis is associated with B cell activating factor in mammary epithelial cells. Exp. Cell Res. 292:115-122 https://doi.org/10.1016/j.yexcr.2003.08.004
  31. Strasser, A., A. W. Harris and S. Cory. 1991. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67:889-899 https://doi.org/10.1016/0092-8674(91)90362-3
  32. Topper, Y. J. and C. S. Freeman. 1980. Multiple hormone interactions in the developmental biology of the mammary gland. Physiol. Rev. 60:1049-1060 https://doi.org/10.1152/physrev.1980.60.4.1049
  33. Wu, G. S., P. Saftig, C. Peters and W. S. El-Deiry. 1998. Potential role for cathepsin D in p53-dependent tumor suppression and chemosensitivity. Oncogene 16:2177-2183 https://doi.org/10.1038/sj.onc.1201755

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Acknowledgement

Supported by : Chonnam National University