دورية أكاديمية
MYC selects against reduced BCL2A1/A1 protein expression during B cell lymphomagenesis.
العنوان: | MYC selects against reduced BCL2A1/A1 protein expression during B cell lymphomagenesis. |
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المؤلفون: | Sochalska M; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Schuler F; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Weiss JG; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Prchal-Murphy M; Institute of Pharmacology and Toxicology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria., Sexl V; Institute of Pharmacology and Toxicology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria., Villunger A; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; Tyrolean Cancer Research Institute, Innsbruck, Austria. |
المصدر: | Oncogene [Oncogene] 2017 Apr; Vol. 36 (15), pp. 2066-2073. Date of Electronic Publication: 2016 Oct 03. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
مواضيع طبية MeSH: | Lymphoma, B-Cell/*genetics , Minor Histocompatibility Antigens/*genetics , Proto-Oncogene Proteins c-bcl-2/*genetics , Proto-Oncogene Proteins c-myc/*genetics, Animals ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Lymphoma, B-Cell/metabolism ; Lymphoma, B-Cell/pathology ; Mice ; Mice, Transgenic ; Minor Histocompatibility Antigens/biosynthesis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Proto-Oncogene Proteins c-myc/biosynthesis |
مستخلص: | Rearrangements of MYC or ABL proto-oncogenes lead to deregulated expression of key-regulators of cell cycle and cell survival, thereby constituting important drivers of blood cancer. Members of the BCL-2 family of apoptosis regulators contribute to oncogenic transformation downstream of these oncogenes, but the role of anti-apoptotic BCL2A1/A1 in transformation and drug resistance caused by deregulation of these oncogenes remains enigmatic. Here we analyzed the role of A1 in MYC as well as ABL kinase-driven blood cancer in mice, employing in vivo RNAi. We report that overexpression of either oncogene leads to a significant increase in A1 protein levels in otherwise A1-negative B cell progenitors, indicating a key role downstream of these oncogenes to secure survival during transformation. Knockdown of A1 by RNAi, however, did not impact on tumor latency in v-Abl-driven pre-B-ALL. In contrast, A1 knockdown in premalignant Eμ-MYC mice caused a significant reduction of transgenic pre-B cells without impacting on tumor latency as the emerging lymphomas escaped silencing of A1 expression. These findings identify A1 as a MYC target that can be induced prematurely during B cell development to aid expansion of otherwise cell-death-prone MYC transgenic pre-B cells. Hence, A1 should be considered as a putative drug target in MYC-driven blood cancer. |
References: | Cancer Cell. 2007 Aug;12 (2):171-85. (PMID: 17692808) Cell Death Differ. 2016 Feb;23 (2):303-12. (PMID: 26184912) Oncogene. 2009 Mar 5;28(9):1274-9. (PMID: 19137012) Blood. 2011 Dec 8;118(24):6380-6. (PMID: 21998213) Blood. 2012 Jun 21;119(25):6032-42. (PMID: 22581448) J Immunol. 2015 Feb 1;194(3):1316-22. (PMID: 25548219) Int J Cancer. 2005 Feb 20;113(5):730-7. (PMID: 15499630) Genes Dev. 2012 Jan 15;26(2):120-5. (PMID: 22279045) EMBO Mol Med. 2010 Mar;2(3):98-110. (PMID: 20201032) Blood. 1999 Sep 15;94(6):1855-63. (PMID: 10477714) J Virol. 2006 Aug;80(16):8133-44. (PMID: 16873269) Semin Hematol. 2014 Jul;51(3):219-27. (PMID: 25048785) FEBS J. 2015 Mar;282(5):834-49. (PMID: 25559680) Blood. 2010 Apr 29;115(17 ):3559-69. (PMID: 20185581) Cell Death Dis. 2016 Feb 18;7:e2103. (PMID: 26890142) Blood. 2013 Sep 26;122(13):2167-75. (PMID: 23926299) Nature. 1985 Dec 12-18;318(6046):533-8. (PMID: 3906410) Blood. 2007 Jun 1;109(11):4907-13. (PMID: 17317859) Cell Death Differ. 2015 Jul;22(7):1071-80. (PMID: 25952548) Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4321-6. (PMID: 23447565) Blood. 2009 Apr 30;113(18):4403-13. (PMID: 19008458) Int Immunol. 1998 May;10 (5):631-7. (PMID: 9645611) Cell Death Differ. 2016 Apr;23 (4):628-39. (PMID: 26450454) Cell Death Differ. 2012 Jan;19(1):67-74. (PMID: 22075983) Cell Death Dis. 2014 Dec 04;5:e1553. (PMID: 25476901) Blood. 2010 Apr 22;115(16):3304-13. (PMID: 20197552) Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14907-12. (PMID: 16997913) Mol Cell Biol. 2001 Aug;21(15):5063-70. (PMID: 11438662) Cell Rep. 2014 Sep 11;8(5):1347-53. (PMID: 25176652) Nature. 2005 Jun 2;435(7042):677-81. (PMID: 15902208) Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17834-9. (PMID: 17093053) Genes Dev. 2014 Jan 1;28(1):58-70. (PMID: 24395247) Exp Cell Res. 2012 Jul 1;318(11):1291-303. (PMID: 22342458) |
المشرفين على المادة: | 0 (BCL2-related protein A1) 0 (Minor Histocompatibility Antigens) 0 (Myc protein, mouse) 0 (Proto-Oncogene Proteins c-bcl-2) 0 (Proto-Oncogene Proteins c-myc) |
تواريخ الأحداث: | Date Created: 20161004 Date Completed: 20170419 Latest Revision: 20210109 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5395700 |
DOI: | 10.1038/onc.2016.362 |
PMID: | 27694901 |
قاعدة البيانات: | MEDLINE |
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