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International Journal of Breast Cancer
Volume 2011 (2011), Article ID 595092, 7 pages
http://dx.doi.org/10.4061/2011/595092
Review Article

Autophagy: Friend or Foe in Breast Cancer Development, Progression, and Treatment

Research Area, Institute of Oncology “Angel H. Roffo”, University of Buenos Aires, C1417DTB Buenos Aires, Argentina

Received 29 April 2011; Accepted 11 July 2011

Academic Editor: Federico Coluccio Leskow

Copyright © 2011 Damian E. Berardi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Fujishima, S. Nishiumi, A. Masuda et al., “Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation,” Archives of Biochemistry and Biophysics, 2011. View at Publisher · View at Google Scholar · View at PubMed
  2. S. Turcotte and A. J. Giaccia, “Targeting cancer cells through autophagy for anticancer therapy,” Current Opinion in Cell Biology, vol. 22, no. 2, pp. 246–251, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. D. J. Klionsky and S. D. Emr, “Autophagy as a regulated pathway of cellular degradation,” Science, vol. 290, no. 5497, pp. 1717–1721, 2000. View at Publisher · View at Google Scholar · View at Scopus
  4. B. Levine and D. J. Klionsky, “Development by self-digestion: molecular mechanisms and biological functions of autophagy,” Developmental Cell, vol. 6, no. 4, pp. 463–477, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Shimizu, T. Kanaseki, N. Mizushima et al., “Role of Bcl-2 family proteins in a non-apoptopic programmed cell death dependent on autophagy genes,” Nature Cell Biology, vol. 6, no. 12, pp. 1221–1228, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. T. Shintani and D. J. Klionsky, “Autophagy in health and disease: a double-edged sword,” Science, vol. 306, no. 5698, pp. 990–995, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. F. Borellini and T. Oka, “Growth control and differentiation in mammary epithelial cells,” Environmental Health Perspectives, vol. 80, pp. 85–99, 1989. View at Google Scholar · View at Scopus
  8. L. H. Quarrie, C. V. P. Addey, and C. J. Wilde, “Apoptosis in lactating and involuting mouse mammary tissue demonstrated by nick-end DNA labelling,” Cell and Tissue Research, vol. 281, no. 3, pp. 413–419, 1995. View at Publisher · View at Google Scholar · View at Scopus
  9. L. H. Quarrie, C. V. P. Addey, and C. J. Wilde, “Programmed cell death during mammary tissue involution induced by weaning, litter removal, and milk stasis,” Journal of Cellular Physiology, vol. 168, no. 3, pp. 559–569, 1996. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Zarzyńska, B. Gajkowska, U. Wojewódzka, E. Dymnicki, and T. Motyl, “Apoptosis and autophagy in involuting bovine mammary gland is accompanied by up-regulation of TGF-β1 and suppression of somatotropic pathway,” Polish Journal of Veterinary Sciences, vol. 10, no. 1, pp. 1–9, 2007. View at Google Scholar · View at Scopus
  11. T. Motyl, M. Gajewska, J. Zarzynska, A. Sobolewska, and B. Gajkowska, “Regulation of autophagy in bovine mammary epithelial cells,” Autophagy, vol. 3, no. 5, pp. 484–486, 2007. View at Google Scholar · View at Scopus
  12. M. Gajewska, A. Sobolewska, M. Kozlowski, and T. Motyl, “Role of autophagy in mammary gland development,” Journal of Physiology and Pharmacology, vol. 59, supplement 9, pp. 237–249, 2008. View at Google Scholar
  13. N. Mizushima and T. Yoshimori, “How to interpret LC3 immunoblotting,” Autophagy, vol. 3, no. 6, pp. 542–545, 2007. View at Google Scholar · View at Scopus
  14. Y. Kabeya, N. Mizushima, T. Ueno et al., “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing,” EMBO Journal, vol. 19, no. 21, pp. 5720–5728, 2000. View at Google Scholar · View at Scopus
  15. S. V. Holt, B. Wyspianska, K. J. Randall, D. James, J. R. Foster, and R. W. Wilkinson, “The development of an immunohistochemical method to detect the autophagy associated protein LC3-II in human tumor xenografts,” Toxicologic Pathology, vol. 39, no. 3, pp. 516–523, 2011. View at Google Scholar
  16. D. J. Klionsky, H. Abeliovich, P. Agostinis et al., “Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes,” Autophagy, vol. 4, no. 2, pp. 151–175, 2008. View at Google Scholar · View at Scopus
  17. I. Tanida, N. Minematsu-Ikeguchi, T. Ueno, and E. Kominami, “Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy,” Autophagy, vol. 1, no. 2, pp. 84–91, 2005. View at Google Scholar · View at Scopus
  18. S. Kimura, N. Fujita, T. Noda, and T. Yoshimori, “Monitoring autophagy in mammalian cultured cells through the dynamics of LC3,” Methods in Enzymology, vol. 451, pp. 1–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. X. Qu, J. Yu, G. Bhagat et al., “Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1809–1820, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Kondo, T. Kanzawa, R. Sawaya, and S. Kondo, “The role of autophagy in cancer development and response to therapy,” Nature Reviews Cancer, vol. 5, no. 9, pp. 726–734, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. X. H. Liang, S. Jackson, M. Seaman et al., “Induction of autophagy and inhibition of tumorigenesis by beclin 1,” Nature, vol. 402, no. 6762, pp. 672–676, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. V. M. Aita, X. H. Liang, V. V. V. S. Murty et al., “Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21,” Genomics, vol. 59, no. 1, pp. 59–65, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. K. Koneri, T. Goi, Y. Hirono, K. Katayama, and A. Yamaguchi, “Beclin 1 gene inhibits tumor growth in colon cancer cell lines,” Anticancer Research, vol. 27, no. 3 B, pp. 1453–1457, 2007. View at Google Scholar · View at Scopus
  24. C. Miracco, E. Cosci, G. Oliveri et al., “Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours,” International Journal of Oncology, vol. 30, no. 2, pp. 429–436, 2007. View at Google Scholar · View at Scopus
  25. T. Kirisako, M. Baba, N. Ishihara et al., “Formation process of autophagosome is traced with Apg8/Aut7p in yeast,” Journal of Cell Biology, vol. 147, no. 2, pp. 435–446, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. L. Moretti, A. Attia, K. W. Kim, and B. Lu, “Crosstalk between Bak/bax and mTOR signaling regulates radiation-induced autophagy,” Autophagy, vol. 3, no. 2, pp. 142–144, 2007. View at Google Scholar · View at Scopus
  27. S. Yousefi, R. Perozzo, I. Schmid et al., “Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis,” Nature Cell Biology, vol. 8, no. 10, pp. 1124–1132, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. Z. Feng, H. Zhang, A. J. Levine, and S. Jin, “The coordinate regulation of the p53 and mTOR pathways in cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 23, pp. 8204–8209, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. U. Akar, B. Ozpolat, K. Mehta, J. Fok, Y. Kondo, and G. Lopez-Berestein, “Tissue transglutaminase inhibits autophagy in pancreatic cancer cells,” Molecular Cancer Research, vol. 5, no. 3, pp. 241–249, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. S. Paglin, T. Hollister, T. Delohery et al., “A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles,” Cancer Research, vol. 61, no. 2, pp. 439–444, 2001. View at Google Scholar · View at Scopus
  31. P. Boya, R. A. González-Polo, N. Casares et al., “Inhibition of macroautophagy triggers apoptosis,” Molecular and Cellular Biology, vol. 25, no. 3, pp. 1025–1040, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. M. A. Qadir, B. Kwok, W. H. Dragowska et al., “Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization,” Breast Cancer Research and Treatment, vol. 112, no. 3, pp. 389–403, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. J. S. Carew, S. T. Nawrocki, C. N. Kahue et al., “Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHAto overcome Bcr-Abl-mediated drug resistance,” Blood, vol. 110, no. 1, pp. 313–322, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. R. K. Amaravadi, D. Yu, J. J. Lum et al., “Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma,” Journal of Clinical Investigation, vol. 117, no. 2, pp. 326–336, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. M. J. Abedin, D. Wang, M. A. McDonnell, U. Lehmann, and A. Kelekar, “Autophagy delays apoptotic death in breast cancer cells following DNA damage,” Cell Death and Differentiation, vol. 14, no. 3, pp. 500–510, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. K. R. Mills, M. Reginato, J. Debnath, B. Queenan, and J. S. Brugge, “Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 10, pp. 3438–3443, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. D. Kim, G. Z. Cheng, C. W. Lindsley, H. Yang, and J. Q. Cheng, “Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer,” Current Opinion in Investigational Drugs, vol. 6, no. 12, pp. 1250–1258, 2005. View at Google Scholar
  38. D. Meley, C. Bauvy, J. H. P. M. Houben-Weerts et al., “AMP-activated protein kinase and the regulation of autophagic proteolysis,” Journal of Biological Chemistry, vol. 281, no. 46, pp. 34870–34879, 2006. View at Publisher · View at Google Scholar · View at PubMed
  39. J. S. Carew, S. T. Nawrocki, and J. L. Cleveland, “Modulating autophagy for therapeutic benefit,” Autophagy, vol. 3, no. 5, pp. 464–467, 2007. View at Google Scholar
  40. M. Buzzai, R. G. Jones, R. K. Amaravadi et al., “Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth,” Cancer Research, vol. 67, no. 14, pp. 6745–6752, 2007. View at Publisher · View at Google Scholar · View at PubMed
  41. G. Yogalingam and A. M. Pendergast, “Abl kinases regulate autophagy by promoting the trafficking and function of lysosomal components,” Journal of Biological Chemistry, vol. 283, no. 51, pp. 35941–35953, 2008. View at Publisher · View at Google Scholar · View at PubMed
  42. T. Kanzawa, L. Zhang, L. Xiao, I. M. Germano, Y. Kondo, and S. Kondo, “Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3,” Oncogene, vol. 24, no. 6, pp. 980–991, 2005. View at Publisher · View at Google Scholar · View at PubMed
  43. M. Høyer-Hansen, L. Bastholm, P. Szyniarowski et al., “Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2,” Molecular Cell, vol. 25, no. 2, pp. 193–205, 2007. View at Publisher · View at Google Scholar · View at PubMed
  44. A. D. Balgi, B. D. Fonseca, E. Donohue et al., “Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling,” PLoS ONE, vol. 4, no. 9, article e7124, 2009. View at Publisher · View at Google Scholar · View at PubMed
  45. C. S. Beevers, L. Chen, L. Liu, Y. Luo, N. J. G. Webster, and S. Huang, “Curcumin disrupts the mammalian target of rapamycin-raptor complex,” Cancer Research, vol. 69, no. 3, pp. 1000–1008, 2009. View at Publisher · View at Google Scholar · View at PubMed
  46. C. Cao, T. Subhawong, J. M. Albert et al., “Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells,” Cancer Research, vol. 66, no. 20, pp. 10040–10047, 2006. View at Publisher · View at Google Scholar · View at PubMed
  47. V. Y. Yazbeck, D. Buglio, G. V. Georgakis et al., “Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma,” Experimental Hematology, vol. 36, no. 4, pp. 443–450, 2008. View at Publisher · View at Google Scholar · View at PubMed
  48. M. A. Park, G. Zhang, A. P. Martin et al., “Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation,” Cancer Biology and Therapy, vol. 7, no. 10, pp. 1648–1662, 2008. View at Google Scholar
  49. P. M. Yang and C. C. Chen, “Life or death? Autophagy in anticancer therapies with statins and histone deacetylase inhibitors,” Autophagy, vol. 7, no. 1, pp. 107–108, 2011. View at Publisher · View at Google Scholar
  50. M. P. Cole, C. T. Jones, and I. D. Todd, “A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474,” British Journal of Cancer, vol. 25, no. 2, pp. 270–275, 1971. View at Google Scholar
  51. R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar, “Cellular and molecular pharmacology of antiestrogen action and resistance,” Pharmacological Reviews, vol. 53, no. 1, pp. 25–71, 2001. View at Google Scholar
  52. R. B. Riggins, A. H. Bouton, M. C. Liu, and R. Clarke, “Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer,” Vitamins and Hormones, vol. 71, pp. 201–237, 2005. View at Publisher · View at Google Scholar · View at PubMed
  53. K. B. Bouker, T. C. Skaar, D. R. Fernandez et al., “Interferon regulatory factor-1 mediates the proapoptotic but not cell cycle arrest effects of the steroidal antiestrogen ICI 182,780 (Faslodex, Fulvestrant),” Cancer Research, vol. 64, no. 11, pp. 4030–4039, 2004. View at Publisher · View at Google Scholar · View at PubMed
  54. N. Török, R. Urrutia, T. Nakamura, and M. A. McNiven, “Upregulation of molecular motor-encoding genes during hepatocyte growth factor-and epidermal growth factor-induced cell motility,” Journal of Cellular Physiology, vol. 167, no. 3, pp. 422–433, 1996. View at Google Scholar
  55. B. Inbal, S. Bialik, I. Sabanay, G. Shani, and A. Kimchi, “DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death,” Journal of Cell Biology, vol. 157, no. 3, pp. 455–468, 2002. View at Publisher · View at Google Scholar · View at PubMed
  56. R. Clarke, A. N. Shajahan, R. B. Riggins et al., “Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells,” Journal of Steroid Biochemistry and Molecular Biology, vol. 114, no. 1-2, pp. 8–20, 2009. View at Publisher · View at Google Scholar
  57. N. Brunner, T. L. Frandsen, C. Holst-Hansen et al., “MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780,” Cancer Research, vol. 53, no. 14, pp. 3229–3232, 1993. View at Google Scholar
  58. N. Brünner, B. Boysen, S. Jirus et al., “MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross- resistance to the nonsteroidal antiestrogen tamoxifen,” Cancer Research, vol. 57, no. 16, pp. 3486–3493, 1997. View at Google Scholar
  59. N. Brunner, V. Boulay, A. Fojo, C. E. Freter, M. E. Lippman, and R. Clarke, “Acquisition of hormone-independent growth in MCF-7 cells is accompanied by increased expression of estrogen-regulated genes but without detectable DNA amplifications,” Cancer Research, vol. 53, no. 2, pp. 283–290, 1993. View at Google Scholar
  60. J. Adams, V. J. Palombella, E. A. Sausville et al., “Proteasome inhibitors: a novel class of potent and effective antitumor agents,” Cancer Research, vol. 59, no. 11, pp. 2615–2622, 1999. View at Google Scholar
  61. T. Caravita, P. de Fabritiis, A. Palumbo, S. Amadori, and M. Boccadoro, “Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies,” Nature Clinical Practice Oncology, vol. 3, no. 7, pp. 374–387, 2006. View at Publisher · View at Google Scholar · View at PubMed
  62. S. T. Nawrocki, J. S. Carew, M. S. Pino et al., “Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis,” Cancer Research, vol. 65, no. 24, pp. 11658–11666, 2005. View at Publisher · View at Google Scholar · View at PubMed
  63. T. Rzymski and A. L. Harris, “The unfolded protein response and integrated stress response to anoxia,” Clinical Cancer Research, vol. 13, no. 9, pp. 2537–2540, 2007. View at Publisher · View at Google Scholar · View at PubMed
  64. H. P. Harding, Y. Zhang, and D. Ron, “Protein translation and folding are coupled by an endoplasmic- reticulum-resident kinase,” Nature, vol. 397, no. 6716, pp. 271–274, 1999. View at Publisher · View at Google Scholar · View at PubMed
  65. T. Yorimitsu and D. J. Klionsky, “Endoplasmic reticulum stress: a new pathway to induce aytophagy,” Autophagy, vol. 3, no. 2, pp. 160–162, 2007. View at Google Scholar
  66. T. Yorimitsu, U. Nair, Z. Yang, and D. J. Klionsky, “Endoplasmic reticulum stress triggers autophagy,” Journal of Biological Chemistry, vol. 281, no. 40, pp. 30299–30304, 2006. View at Publisher · View at Google Scholar · View at PubMed
  67. Y. Kouroku, E. Fujita, I. Tanida et al., “ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation,” Cell Death and Differentiation, vol. 14, no. 2, pp. 230–239, 2007. View at Publisher · View at Google Scholar · View at PubMed
  68. M. Milani, T. Rzymski, H. R. Mellor et al., “The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib,” Cancer Research, vol. 69, no. 10, pp. 4415–4423, 2009. View at Publisher · View at Google Scholar · View at PubMed
  69. M. D. Pegram, G. Konecny, and D. J. Slamon, “The molecular and cellular biology of HER2/neu gene amplification/overexpression and the clinical development of herceptin (trastuzumab) therapy for breast cancer,” Cancer Treatment and Research, vol. 103, pp. 57–75, 2000. View at Google Scholar
  70. K. H. Lan, C. H. Lu, and D. Yu, “Mechanisms of trastuzumab resistance and their clinical implications,” Annals of the New York Academy of Sciences, vol. 1059, pp. 70–75, 2005. View at Publisher · View at Google Scholar · View at PubMed
  71. R. Nahta and F. J. Esteva, “Herceptin: mechanisms of action and resistance,” Cancer Letters, vol. 232, no. 2, pp. 123–138, 2006. View at Publisher · View at Google Scholar · View at PubMed
  72. R. Nahta, D. Yu, M. C. Hung, G. N. Hortobagyi, and F. J. Esteva, “Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer,” Nature Clinical Practice Oncology, vol. 3, no. 5, pp. 269–280, 2006. View at Publisher · View at Google Scholar · View at PubMed
  73. R. Nahta and F. J. Esteva, “Trastuzumab: triumphs and tribulations,” Oncogene, vol. 26, no. 25, pp. 3637–3643, 2007. View at Publisher · View at Google Scholar · View at PubMed
  74. S. A. Price-Schiavi, S. Jepson, P. Li et al., “Rat MUC4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance,” International Journal of Cancer, vol. 99, no. 6, pp. 783–791, 2002. View at Publisher · View at Google Scholar · View at PubMed
  75. P. Nagy, E. Friedländer, M. Tanner et al., “Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing cancer cell line,” Cancer Research, vol. 65, no. 2, pp. 473–482, 2005. View at Google Scholar
  76. A. Vazquez-Martin, C. Oliveras-Ferraros, and J. A. Menendez, “Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab,” PLoS ONE, vol. 4, no. 7, article e6251, 2009. View at Publisher · View at Google Scholar · View at PubMed
  77. Y. Yu, F. Xu, H. Peng et al., “NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 1, pp. 214–219, 1999. View at Publisher · View at Google Scholar
  78. L. Wang, A. Hoque, R. Z. Luo et al., “Loss of the expression of the tumor suppressor gene ARHI is associated with progression of breast cancer,” Clinical Cancer Research, vol. 9, no. 10 I, pp. 3660–3666, 2003. View at Google Scholar
  79. C. F. Zou, L. Jia, H. Jin et al., “Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel,” BMC Cancer, vol. 11, p. 22, 2011. View at Google Scholar