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Bcl-2 Gene Family and Related Proteins in Mammary Gland Involution and Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The Bcl-2 gene family regulates tissuedevelopment and tissue homeostasis through the interplayof survival and death factors. Family members arecharacterized as either pro-apoptotic or anti-apoptotic, depending on cellular context. In addition toits anti-apoptotic effect, Bcl-2 also inhibitsprogression through the cell cycle. Functionalinteractions between family members as well as bindingto other cellular proteins modulate their activities.Mammary gland tissue, similar to many other tissues,expresses a number of different Bcl-2 relativesincluding bclx, bax, bak, bad, bcl-w, bfl-1, bcl-2 aswell as the bcl-2 binding protein Bag-1. Bcl-2 isexpressed in the nonpregnant mammary gland and earlypregnancy. In contrast, expression of bcl-x and baxcontinues through late pregnancy, is down-regulated during lactation, and upregulated with thestart of involution. Bak, bad, bcl-w, and bfl-1 are alsoup-regulated during involution. The specific roles ofindividual gene products are investigated using dominant gain of function and loss of functionmice. Finally, different Bcl-2 family members arecommonly over- or under-expressed in human breastcancers. Bcl-2 expression in human breast cancers hasbeen associated with a good prognosis, whiledecreased Bax expression has been linked to poorclinical outcome. Understanding the role Bcl-2 familymembers play in regulating mammary epithelial cellsurvival is salient to both normal mammary glandphysiology and the development of new therapeuticapproaches to breast cancer.

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REFERENCES

  1. J. M. Adams and S. Cory (1998). The Bcl-2 protein family: Arbiters of cell survival. Science 281:1322–1326.

    Google Scholar 

  2. Y. Tsujimoto, L. R. Finger, J. Yunis, P. C. Nowell, and C. M. Croce (1984). Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226:1097–1099.

    Google Scholar 

  3. S. J. Korsmeyer (1992). Bcl-2 initiates a new category of oncogenes: Regulators of cell death. Blood 80:879–886.

    Google Scholar 

  4. T. J. McDonnell and S. J. Korsmeyer (1991). Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature 349:254–256.

    Google Scholar 

  5. Z. N. Oltvai and S. J. Korsmeyer (1994). Checkpoints of dueling dimers foil death wishes [comment]. Cell 79:189–192.

    Google Scholar 

  6. G. T. Williams and C. A. Smith (1993). Molecular regulation of apoptosis: Genetic controls on cell death. Cell 74:777–779.

    Google Scholar 

  7. S. J. Korsmeyer (1995). Regulators of cell death. Trends Genet 11:101–105.

    Google Scholar 

  8. X. M. Yin, Z. N. Oltvai, and S. J. Korsmeyer (1994). BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax [see comments]. Nature 369:321–323.

    Google Scholar 

  9. T. Chittenden, C. Flemington, A. B. Houghton, R. G. Ebb, G. J. Gallo, B. Elangovan, G. Chinnadurai, and R. J. Lutz (1995). A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 14:5589–5596.

    Google Scholar 

  10. D. T. Chao and S. J. Korsmeyer (1998). BCL-2 family: Regulators of cell death. Ann. Rev. Immunol. 16:395–419.

    Google Scholar 

  11. S. J. Korsmeyer, J. R. Shutter, D. J. Veis, D. E. Merry, and Z. N. Oltvai (1993). Bcl-2/Bax: A rheostat that regulates an anti-oxidant pathway and cell death. Semin. Cancer Biol. 4: 327–332.

    Google Scholar 

  12. W. Zhu, A. Cowie, G. W. Wasfy, L. Z. Penn, B. Leber, and D. W. Andrews (1996). Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. EMBO J. 15:4130–4141.

    Google Scholar 

  13. H. Zha, H. A. Fisk, M. P. Yaffe, N. Mahajan, B. Herman, and J.:C. Reed (1996). Structure-function comparisons of the proapoptotic protein Bax in yeast and mammalian cells. Mol. Cell Biol. 16:6494–6508.

    Google Scholar 

  14. D. R. Green and J. C. Reed (1998). Mitochondria and apoptosis. Science 281:1309–1312.

    Google Scholar 

  15. J. C. Reed (1997). Double identity for proteins of the Bcl-2 family. Nature 387:773–776.

    Google Scholar 

  16. R. M. Kluck, E. Bossy-Wetzel, D. R. Green, and D. D. Newmeyer (1997). The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis. Science 275: 1132–1136.

    Google Scholar 

  17. J. Yang, X. Liu, K. Bhalla, C. N. Kim, A. M. Ibrado, J. Cai, T. I. Peng, D. P. Jones, and X. Wang (1997). Prevention of apoptosis by Bcl-2: Release of cytochrome c from mitochondria blocked. Science 275:1129–1132.

    Google Scholar 

  18. X. Liu, C. N. Kim, J. Yang, R. Jemmerson, and X. Wang (1996). Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 86:147–157.

    Google Scholar 

  19. T. Rosse, R. Olivier, L. Monney, M. Rager, S. Conus, I. Fellay, B. Jansen, and C. Borner (1998). Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 391: 496–499.

    Google Scholar 

  20. J. Zha, H. Harada, E. Yang, J. Jockel, and S. J. Korsmeyer (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14–3–3 not BCL-X(L). Cell 87:619–628.

    Google Scholar 

  21. E. Yang, J. Zha, J. Jockel, L. H. Boise, C. B. Thompson, and S. J. Korsmeyer (1995). Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 80:285–291.

    Google Scholar 

  22. S. Haldar, N. Jena, and C. M. Croce (1995). Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 92: 4507–4511.

    Google Scholar 

  23. S. Takayama, T. Sato, S. Krajewski, K. Kochel, S. Irie, J. A. Millan, and J. C. Reed (1995). Cloning and functional analysis of BAG-1: A novel Bcl-2–binding protein with anti-cell death activity. Cell 80:279–284.

    Google Scholar 

  24. S. Takayama, D. N. Bimston, S. Matsuzawa, B. C. Freeman, C. Aime-Sempe, Z. Xie, R. I. Morimoto, and J. C. Reed (1997). BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 16:4887–4896.

    Google Scholar 

  25. G. Pan, K. O'Rourke, and V. M. Dixit (1998). Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J. Biol. Chem. 273: 5841–5845.

    Google Scholar 

  26. L. A. O'Reilly, D. C. Huang, and A. Strasser (1996). The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry. EMBO J. 15:6979–6990.

    Google Scholar 

  27. D. C. Huang, L. A. O'Reilly, A. Strasser, and S. Cory (1997). The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry. EMBO J. 16:4628–4638.

    Google Scholar 

  28. W. S. el-Deiry, J. W. Harper, P. M. O'Connor, V. E. Velculescu, C. E. Canman, J. Jackman, J. A. Pietenpol, M. Burrell, D. E. Hill, and Y. Wang (1994). WAF1/CIP1 is induced in p53–mediated G1 arrest and apoptosis. Cancer Res. 54:1169–1174.

    Google Scholar 

  29. C. Borner (1996). Diminished cell proliferation associated with the death-protective activity of Bcl-2. J. Biol. Chem. 271: 12695–12698.

    Google Scholar 

  30. E. J. Uhlmann, C. D'Sa-Eipper, T. Subramanian, A. J. Wagner, N. Hay, and G. Chinnadurai (1996). Deletion of a nonconserved region of Bcl-2 confers a novel gain of function: Suppression of apoptosis with concomitant cell proliferation. Cancer Res. 56:2506–2509.

    Google Scholar 

  31. G. Gil-Gomez, A. Berns, and H. J. Brady (1998). A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J. 17:7209–7218.

    Google Scholar 

  32. G. P. Linette, Y. Li, K. Roth, and S. J. Korsmeyer (1996). Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc. Natl. Acad. Sci. U.S.A. 93:9545–9552.

    Google Scholar 

  33. P. A. Furth, U. Bar-Peled, M. Li, A. Lewis, R. Laucerica, R. Jager, H. Weiher, and R. Russell (1999). Loss of anti-mitotic activity of Bcl-2 with retention of anti-apoptotic function during tumor progression in a mouse model. (Submitted).

  34. K. L. Murphy, F. S. Kittrell, J. P. Gay, R. Jaeger, D. Medina, and J. M. Rosen (1999). Bcl-2 expression inhibits mammary tumor development in dimethylbenz(a) anthracene-treat ed transgenic mice. (Submitted).

  35. R. C. Humphreys (1999). Programmed cell death in the terminal endbud. J. Mam. Gland Biol. Neoplasia 4:XXX-XXX

    Google Scholar 

  36. R. C. Humphreys, M. Krajewska, S. Krnacik, R. Jaeger, H. Weiher, S. Krajewski, J. C. Reed, and J.M. Rosen (1996). Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of ductal morphogenesis. Development 122:4013–4022.

    Google Scholar 

  37. K. Heermeier, M. Benedict, M. Li, P. Furth, G. Nunez, and L. Hennighausen (1996). Bax and Bcl-xs are induced at the onset of apoptosis in involuting mammary epithelial cells. Mech. Dev. 56:197–207.

    Google Scholar 

  38. S. Pullan, J. Wilson, A. Metcalfe, G. M. Edwards, N. Goberdhan, J. Tilly, J. A. Hickman, C. Dive, and C. H. Streuli (1996). Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. J. Cell Sci. 109:631–642.

    Google Scholar 

  39. R. C. Bargou, P. T. Daniel, M. Y. Mapara, K. Bommert, C. Wagener, B. Kallinich, H. D. Royer, and B. Dorken (1995). Expression of the bcl-2 gene family in normal and malignant breast tissue: Low bax-alpha expression in tumor cells correlates with resistance towards apoptosis. Int. J. Cancer 60: 854–859.

    Google Scholar 

  40. J. M. Gee, J. F. Robertson, I. O. Ellis, P. Willsher, R. A. McClelland, H. B. Hoyle, S. R. Kyme, P. Finlay, R. W. Blamey, and R. I. Nicholson (1994). Immunocytochem ical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. Int. J. Cancer 59:619–628.

    Google Scholar 

  41. G. J. Zhang, I. Kimijima, A. Tsuchiya, and R. Abe (1998). The role of bcl-2 expression in breast carcinomas (Review). Oncol. Rep. 5:1211–1216.

    Google Scholar 

  42. M. Li, J. Hu, K. Heermeier, L. Hennighausen, and P. A. Furth (1996). Expression of a viral oncoprotein during mammary gland development alters cell fate and function: Induction of p53–independent apoptosis is followed by impaired milk protein production in surviving cells. Cell Growth Differ. 7: 3–11.

    Google Scholar 

  43. M. Li, J. Hu, K. Heermeier, L. Hennighausen, and P. A. Furth (1996). Apoptosis and remodeling of mammary gland tissue during involution proceeds through p53–independent pathways. Cell Growth Differ. 7:13–20.

    Google Scholar 

  44. A. Sierra, X. Castellsague, T. Coll, S. Manas, A. Escobedo, A. Moreno, and A. Fabra (1998). Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas. Int. J. Cancer 79:103–110.

    Google Scholar 

  45. S. Kitada, M. Krajewska, X. Zhang, D. Scudiero, J. M. Zapata, H. G. Wang, A. Shabaik, G. Tudor, S. Krajewski, T. G. Myers, G. S. Johnson, E. A. Sausville, and J. C. Reed (1998). Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines. Am. J. Pathol. 152:51–61.

    Google Scholar 

  46. J. M. Zapata, M. Krajewska, S. Krajewski, R. Huang, S. Takayama, H. G. Wang, E. Adamson, and J. C. Reed (1998). Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors. Breast Cancer Res. Treat. 47:129–140.

    Google Scholar 

  47. C. V. Clevenger, K. Thickman, W. Ngo, W. P. Chang, S. Takayama, and J. C. Reed (1997). Role of Bag-1 in the survival and proliferation of the cytokine-dependent lymphocyte lines, Ba/F3 and Nb2. Mol. Endocrinol. 11:608–618.

    Google Scholar 

  48. H. G. Wang, S. Takayama, U. R. Rapp, and J. C. Reed (1996). Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc. Natl. Acad. Sci. U.S.A. 93:7063–7068.

    Google Scholar 

  49. S. Krajewski, M. Krajewska, A. Shabaik, H. G. Wang, S. Irie, L. Fong, and J. C. Reed (1994). Immunohistoche mical analysis of in vivo patterns of Bcl-X expression. Cancer Res. 54: 5501–5507.

    Google Scholar 

  50. D. M. Hockenbery, M. Zutter, W. Hickey, M. Nahm, and S. J. Korsmeyer (1991). BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc. Natl. Acad. Sci. U.S.A. 88:6961–6965.

    Google Scholar 

  51. S. Takayama, S. Krajewski, M. Krajewska, S. Kitada, J. M. Zapata, K. Kochel, D. Knee, D. Scudiero, G. Tudor, G. J. Miller, T. Miyashita, M. Yamada, and J. C. Reed (1998). Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines. Cancer Res. 58:3116–3131.

    Google Scholar 

  52. S. Krajewski, M. Krajewska, A. Shabaik, T. Miyashita, H. G. Wang, and J. C. Reed (1994). Immunohistochem ical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am. J. Pathol. 145:1323–1336.

    Google Scholar 

  53. N. Motoyama, F. Wang, K. A. Roth, H. Sawa, K. Nakayama, I. Negishi, S. Senju, Q. Zhang, and S. Fujii (1995). Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267:1506–1510.

    Google Scholar 

  54. A. Ma, J. C. Pena, B. Chang, E. Margosian, L. Davidson, F. W. Alt, and C. B. Thompson (1995). Bclx regulates the survival of double-positive thymocytes. Proc. Natl. Acad. Sci. U.S.A. 92:4763–4767.

    Google Scholar 

  55. S. Kamada, A. Shimono, Y. Shinto, T. Tsujimura, T. Takahashi, T. Noda, Y. Kitamura, H. Kondoh, and Y. Tsujimoto (1995). Bcl-2 deficiency in mice leads to pleiotropic abnormalities: Accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentati on, and distorted small intestine. Cancer Res. 55:354–359.

    Google Scholar 

  56. D. J. Veis, C. M. Sorenson, J. R. Shutter, and S. J. Korsmeyer (1993). Bcl-2–deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229–240.

    Google Scholar 

  57. V. S. Ratts, J. A. Flaws, R. Kolp, C. M. Sorenson, and J. L. Tilly (1995). Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology 136: 3665–3668.

    Google Scholar 

  58. T. M. Michaelidis, M. Sendtner, J. D. Cooper, M. S. Airaksinen, B. Holtmann, M. Meyer, and H. Thoenen (1996). Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development. Neuron 17:75–89.

    Google Scholar 

  59. K. Nakayama, I. Negishi, K. Kuida, H. Sawa, and D. Y. Loh (1994). Targeted disruption of Bcl-2 alpha beta in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc. Natl. Acad. Sci. U.S.A. 91:3700–3704.

    Google Scholar 

  60. K. Nakayama, I. Negishi, K. Kuida, Y. Shinkai, M. C. Louie, L. E. Fields, P. J. Lucas, V. Stewart, and F. W. Alt (1993). Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice. Science 261:1584–1588.

    Google Scholar 

  61. T. L. Deckwerth, J. L. Elliott, C. M. Knudson, E. M. Johnson, Jr., W. D. Snider, and S. J. Korsmeyer (1996). BAX is required for neuronal death after trophic factor deprivation and during development. Neuron 17:401–411.

    Google Scholar 

  62. F. A. White, C. R. Keller-Peck, C. M. Knudson, S. J. Korsmeyer, and W. D. Snider (1998). Widespread elimination of naturally occurring neuronal death in Bax-deficient mice. J. Neurosci. 18:1428–1439.

    Google Scholar 

  63. C. M. Knudson, K. S. Tung, W. G. Tourtellotte, G. A. Brown, and S. J. Korsmeyer (1995). Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270: 96–99.

    Google Scholar 

  64. C. G. Print, K. L. Loveland, L. Gibson, T. Meehan, A. Stylianou, N. Wreford, D. de Kretser, D. Metcalf, F. Kontgen, J. M. Adams, and S. Cory (1998). Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant [In process citation]. Proc. Natl. Acad. Sci. U.S.A. 95: 12424–12431.

    Google Scholar 

  65. A. J. Ross, K. G. Waymire, J. E. Moss, A. F. Parlow, M. K. Skinner, L. D. Russell, and G. R. MacGregor (1998). Testicular degeneration in Bclw-deficient mice [see comments]. Nat. Genet. 18:251–256.

    Google Scholar 

  66. K. Schorr, U. Bar-Peled, M. Li, A. Lewis, A. Heredia, B. Lewis, C. M. Knudson, S. J. Korsmeyer, R. Jager, H. Weiher, and P. A. Furth, (1999). Gain of Bcl-2 is more potent than Bax loss in regulating mammary epithelial cell survival during tissue remodeling, Cancer Research: (in press).

  67. K. U. Wagner, R. J. Wall, L. St-Onge, P. Gruss, A. Wynshaw-Boris, L. Garrett, M. Li, P. A. Furth, and L. Hennighausen (1997). Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res. 25:4323–4330.

    Google Scholar 

  68. J. Rodriguez-Villanueva, D. Greenhalgh, X. J. Wang, D. Bundman, S. Cho, M. Delehedde, D. Roop, and T. J. McDonnell (1998). Human keratin-1.bcl-2 transgenic mice aberrantly express keratin 6, exhibit reduced sensitivity to keratinocyte cell death induction, and are susceptible to skin tumor formation. Oncogene 16:853–863.

    Google Scholar 

  69. P. Naik, J. Karrim, and D. Hanahan (1996). The rise and fall of apoptosis during multistage tumorigenesis: Down-modulation contributes to tumor progression from angiogenic progenitors. Genes Dev. 10:2105–2116.

    Google Scholar 

  70. R. Jager, U. Herzer, J. Schenkel, and H. Weiher (1997). Over-expression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice. Oncogene 15: 1787–1795.

    Google Scholar 

  71. C. Teixeira, J. C. Reed, and M. A. Pratt (1995). Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Res. 55:3902–3907.

    Google Scholar 

  72. T. T. Wang and J. M. Phang (1995). Effects of estrogen on apoptotic pathways in human breast cancer cell line MCF-7. Cancer Res. 55:2487–2489.

    Google Scholar 

  73. Y. Huang, S. Ray, J. C. Reed, A. M. Ibrado, C. Tang, A. Nawabi, and K. Bhalla (1997). Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells. Breast Cancer Res. Treat. 42:73–81.

    Google Scholar 

  74. D. Delia, A. Aiello, D. Soligo, E. Fontanella, C. Melani, F. Pezzella, M. A. Pierotti, and G. Della Porta (1992). bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood 79:1291–1298.

    Google Scholar 

  75. J. C. Reed (1996). Balancing cell life and death: Bax, apoptosis, and breast cancer [editorial; comment]. J. Clin. Invest. 97: 2403–2404.

    Google Scholar 

  76. J. C. Reed (1994). Bcl-2 and the regulation of programmed cell death. J. Cell. Biol. 124:1–6.

    Google Scholar 

  77. S. Krajewski, C. Blomqvist, K. Franssila, M. Krajewska, V. M. Wasenius, E. Niskanen, S. Nordling, and J.C. Reed (1995). Reduced expression of proapoptotic gene Bax is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res. 55:4471–4478.

    Google Scholar 

  78. A. Marti, Z. Feng, B. Jehn, V. Djonov, G. Chicaiza, H. J. Altermatt, and R. Jaggi (1995). Expression and activity of cell cycle regulators during proliferation and programmed cell death in the mammary gland. Cell Death Differ 2:277–284.

    Google Scholar 

  79. P. Lipponen, T. Pietilainen, V. M. Kosma, S. Aaltomaa, M. Eskelinen, and K. Syrjanen (1995). Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favorable prognosis. J. Pathol. 177:49–55.

    Google Scholar 

  80. S. W. Lowe, H. E. Ruley, T. Jacks, and D. E. Housman (1993). p53–dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967.

    Google Scholar 

  81. L. R. Lund, 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: Proteinase-independent and-dependent pathways. Development 122: 181–193.

    Google Scholar 

  82. R. C. Bargou, C. Wagener, K. Bommert, M. Y. Mapara, P. T. Daniel, W. Arnold, M. Dietel, H. Guski, A. Feller, H. D. Royer, and B. Dorken (1996). Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice [see comments]. J. Clin. Invest. 97:2651–2659.

    Google Scholar 

  83. C. M. Knudson and S. J. Korsmeyer (1997). Bcl-2 and Bax function independently to regulate cell death. Nat. Genet. 16:358–363.

    Google Scholar 

  84. C. Yin, C. M. Knudson, S. J. Korsmeyer, and T. Van Dyke (1997). Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385:637–640.

    Google Scholar 

  85. R. Bernard, S. Dieni, S. Rees, and O. Bernard (1998). Physiological and induced neuronal death are not affected in NSE-bax transgenic mice. J. Neurosci. Res. 52:247–259.

    Google Scholar 

  86. P. G. Farlie, R. Dringen, S. M. Rees, G. Kannourakis, and O. Bernard (1995). bcl-2 transgene expression can protect neurons against developmental and induced cell death. Proc. Natl. Acad. Sci. U.S.A. 92:4397–4401.

    Google Scholar 

  87. J. C. Martinou, M. Dubois-Dauphin, J. K. Staple, I. Rodriguez, H. Frankowski, M. Missotten, P. Albertini, D. Talabot, S. Catsicas, and C. Pietra (1994). Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13:1017–1030.

    Google Scholar 

  88. M. Dubois-Dauphin, H. Frankowski, Y. Tsujimoto, J. Huarte, and J. C. Martinou (1994). Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death. Proc. Natl. Acad. Sci. U.S.A. 91:3309–3313.

    Google Scholar 

  89. D. A. Grillot, R. Merino, J. C. Pena, W. C. Fanslow, F. D. Finkelman, C. B. Thompson, and G. Nunez (1996). Bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J. Exp. Med. 183:381–391.

    Google Scholar 

  90. D. A. Grillot, R. Merino, and G. Nunez (1995).Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice. J. Exp. Med. 182:1973–1983.

    Google Scholar 

  91. J. C. Reed, S. Krajewski, S. Kitada, and T. Miyashita (1998) Methods of measuring Bcl-2 gene expression. In Handbook of Experimental Immunology, Ed. Herzenberg and Weir Blackwell Science, Cambridge.

  92. S. Krajewski, A. Hugger, M. Krajewska, J. C. Reed, and J. K. Mai (1998). Developmental expression patterns of Bcl-2, Bcl-x, Bax, and Bak in teeth. Cell Death Differ. 5: 408–415.

    Google Scholar 

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  1. Kristel Schorr
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  2. Minglin Li
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  3. Stanislaw Krajewski
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  4. John C. Reed
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Schorr, K., Li, M., Krajewski, S. et al. Bcl-2 Gene Family and Related Proteins in Mammary Gland Involution and Breast Cancer. J Mammary Gland Biol Neoplasia 4, 153–164 (1999). https://doi.org/10.1023/A:1018773123899

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