دورية أكاديمية
TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease.
| العنوان: | TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease. |
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| المؤلفون: | Baba M; Laboratory of Cancer Metabolism, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. linehanm@mail.nih.gov schmidtl@mail.nih.gov babam@kumamoto-u.ac.jp.; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Furuya M; Department of Molecular Pathology, Yokohama City University, Yokohama, Japan., Motoshima T; Department of Urology, Kumamoto University, Kumamoto, Japan., Lang M; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Funasaki S; Laboratory of Cancer Metabolism, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan., Ma W; Laboratory of Cancer Metabolism, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan., Sun HW; Biodata Mining and Discovery Section, NIAMS, NIH, Bethesda, Maryland., Hasumi H; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.; Department of Urology, Yokohama City University, Yokohama, Japan., Huang Y; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Kato I; Department of Molecular Pathology, Yokohama City University, Yokohama, Japan., Kadomatsu T; Department of Molecular Genetics, Kumamoto University, Kumamoto, Japan., Satou Y; Laboratory of Retroviral Genomics and Transcriptomics, International Research Center for Medical Sciences (IRCMS), Center for AIDS Research, Kumamoto University, Kumamoto, Japan., Morris N; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Karim BO; Pathology/Histotechnology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Ileva L; Small Animal Imaging Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Kalen JD; Small Animal Imaging Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Wilan Krisna LA; Laboratory of Cancer Metabolism, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan., Hasumi Y; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Sugiyama A; DSK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan., Kurahashi R; Department of Urology, Kumamoto University, Kumamoto, Japan.; Department of Molecular Genetics, Kumamoto University, Kumamoto, Japan., Nishimoto K; Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan., Oyama M; Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan., Nagashima Y; Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan., Kuroda N; Department of Pathology, Kochi Red Cross Hospital, Kochi, Japan., Araki K; Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan., Eto M; Department of Urology, Kyushyu University, Fukuoka, Japan., Yao M; Department of Urology, Yokohama City University, Yokohama, Japan., Kamba T; Department of Urology, Kumamoto University, Kumamoto, Japan., Suda T; Laboratory of Stem Cell Regulation, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore., Oike Y; Department of Molecular Genetics, Kumamoto University, Kumamoto, Japan., Schmidt LS; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. linehanm@mail.nih.gov schmidtl@mail.nih.gov babam@kumamoto-u.ac.jp.; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland., Linehan WM; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. linehanm@mail.nih.gov schmidtl@mail.nih.gov babam@kumamoto-u.ac.jp. |
| المصدر: | Molecular cancer research : MCR [Mol Cancer Res] 2019 Aug; Vol. 17 (8), pp. 1613-1626. Date of Electronic Publication: 2019 May 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101150042 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3125 (Electronic) Linking ISSN: 15417786 NLM ISO Abbreviation: Mol Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, c2002- |
| مواضيع طبية MeSH: | Chromosomes, Human, X* , Oncogene Proteins, Fusion* , Translocation, Genetic*, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics , Carcinoma, Renal Cell/*pathology , Kidney Neoplasms/*pathology , Membrane Glycoproteins/*metabolism, Adolescent ; Adult ; Aged ; Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/metabolism ; Cell Cycle Proteins/genetics ; Cell Proliferation ; Child ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Male ; Membrane Glycoproteins/genetics ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Neoplasm Proteins/genetics ; Prognosis ; Survival Rate ; Tumor Cells, Cultured ; Young Adult |
| مستخلص: | Renal cell carcinoma (RCC) associated with Xp11.2 translocation (TFE3-RCC) has been recently defined as a distinct subset of RCC classified by characteristic morphology and clinical presentation. The Xp11 translocations involve the TFE3 transcription factor and produce chimeric TFE3 proteins retaining the basic helix-loop-helix leucine zipper structure for dimerization and DNA binding suggesting that chimeric TFE3 proteins function as oncogenic transcription factors. Diagnostic biomarkers and effective forms of therapy for advanced cases of TFE3-RCC are as yet unavailable. To facilitate the development of molecular based diagnostic tools and targeted therapies for this aggressive kidney cancer, we generated a translocation RCC mouse model, in which the PRCC-TFE3 transgene is expressed specifically in kidneys leading to the development of RCC with characteristic histology. Expression of the receptor tyrosine kinase Ret was elevated in the kidneys of the TFE3-RCC mice, and treatment with RET inhibitor, vandetanib, significantly suppressed RCC growth. Moreover, we found that Gpnmb (Glycoprotein nonmetastatic B) expression was notably elevated in the TFE3-RCC mouse kidneys as seen in human TFE3-RCC tumors, and confirmed that GPNMB is the direct transcriptional target of TFE3 fusions. While GPNMB IHC staining was positive in 9/9 cases of TFE3-RCC, Cathepsin K, a conventional marker for TFE3-RCC, was positive in only 67% of cases. These data support RET as a potential target and GPNMB as a diagnostic marker for TFE3-RCC. The TFE3-RCC mouse provides a preclinical in vivo model for the development of new biomarkers and targeted therapeutics for patients affected with this aggressive form of RCC. IMPLICATIONS: Key findings from studies with this preclinical mouse model of TFE3-RCC underscore the potential for RET as a therapeutic target for treatment of patients with TFE3-RCC, and suggest that GPNMB may serve as diagnostic biomarker for TFE3 fusion RCC. (©2019 American Association for Cancer Research.) |
| References: | Elife. 2016 Sep 26;5:. (PMID: 27668431) Cytogenet Cell Genet. 1996;75(1):2-6. (PMID: 8995477) Hum Mol Genet. 1996 Sep;5(9):1333-8. (PMID: 8872474) J Natl Cancer Inst. 2008 Jan 16;100(2):140-54. (PMID: 18182616) Eur Urol. 2006 May;49(5):798-805. (PMID: 16442207) Am J Surg Pathol. 2012 May;36(5):654-62. (PMID: 22446944) Cancer Discov. 2012 May;2(5):401-4. (PMID: 22588877) Am J Surg Pathol. 2017 May;41(5):655-662. (PMID: 28296677) Pathogenetics. 2008 Nov 03;1(1):3. (PMID: 19014667) J Bone Miner Res. 2018 Oct;33(10):1785-1798. (PMID: 29893999) PLoS One. 2010 Dec 29;5(12):e15793. (PMID: 21209915) Am J Surg Pathol. 2003 Jun;27(6):750-61. (PMID: 12766578) Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15552-7. (PMID: 17028174) Science. 2009 Jul 24;325(5939):473-7. (PMID: 19556463) Sci Signal. 2012 Jun 12;5(228):ra42. (PMID: 22692423) Am J Surg Pathol. 2013 Oct;37(10):1469-89. (PMID: 24025519) N Engl J Med. 2016 Jan 14;374(2):135-45. (PMID: 26536169) Hum Mol Genet. 2003 Jul 15;12(14):1661-9. (PMID: 12837690) J Pathol. 2013 Apr;229(5):743-754. (PMID: 23288701) Pharmacol Ther. 2017 Nov;179:127-141. (PMID: 28546082) Med Mol Morphol. 2010 Jun;43(2):86-90. (PMID: 20683695) Pathol Int. 2013 Aug;63(8):381-90. (PMID: 23957913) Histol Histopathol. 2012 Feb;27(2):133-40. (PMID: 22207547) Am J Pathol. 2001 Jul;159(1):179-92. (PMID: 11438465) Cancer Genet Cytogenet. 1986 Mar 15;21(2):165-9. (PMID: 3004698) Oncogene. 1997 Oct;15(18):2233-9. (PMID: 9393982) Clin Cancer Res. 2014 Aug 1;20(15):4129-40. (PMID: 24899691) Cell. 2018 Apr 19;173(3):595-610.e11. (PMID: 29656894) Clin Oncol (R Coll Radiol). 2017 May;29(5):316-324. (PMID: 28318881) Hum Genet. 1996 Jul;98(1):16-21. (PMID: 8682500) Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15294-8. (PMID: 8986805) Cell Rep. 2018 Apr 3;23(1):313-326.e5. (PMID: 29617669) Nat Genet. 2003 Jul;34(3):267-73. (PMID: 12808457) Genes Dev. 1994 Nov 15;8(22):2770-80. (PMID: 7958932) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Cytogenet Cell Genet. 1995;71(3):280-4. (PMID: 7587394) Nature. 2013 Jul 4;499(7456):43-9. (PMID: 23792563) Proc Natl Acad Sci U S A. 2003 May 13;100(10):6051-6. (PMID: 12719541) Cancer. 2018 Aug;124(16):3381-3389. (PMID: 29905933) Steroids. 2018 May;133:102-107. (PMID: 29097143) Oncogene. 2001 Jan 4;20(1):48-57. (PMID: 11244503) J Am Soc Nephrol. 2002 Jul;13(7):1837-46. (PMID: 12089379) Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):E1624-31. (PMID: 25775561) Pathology. 2010 Jun;42(4):369-73. (PMID: 20438411) Cancer Sci. 2015 Mar;106(3):315-23. (PMID: 25594584) Clin Cancer Res. 2009 Feb 15;15(4):1170-6. (PMID: 19228722) Cancer Res. 1992 Jan 15;52(2):348-56. (PMID: 1345811) Genes Chromosomes Cancer. 2015 Aug;54(8):500-505. (PMID: 26032162) Am J Surg Pathol. 2007 Aug;31(8):1149-60. (PMID: 17667536) Oncogene. 2003 Aug 14;22(34):5374-8. (PMID: 12917640) Cancer Res. 2017 Feb 15;77(4):897-907. (PMID: 27979841) Am J Surg Pathol. 2013 Jun;37(6):804-15. (PMID: 23598965) Nat Rev Urol. 2014 Aug;11(8):465-75. (PMID: 25048860) Am J Surg Pathol. 2013 Aug;37(8):1150-63. (PMID: 23715164) Am J Surg Pathol. 2002 Dec;26(12):1553-66. (PMID: 12459622) Nat Genet. 2014 Mar;46(3):225-233. (PMID: 24487277) Oncotarget. 2012 Nov;3(11):1472-82. (PMID: 23178531) |
| معلومات مُعتمدة: | HHSN261200800001C United States CA NCI NIH HHS; HHSN261200800001E United States CA NCI NIH HHS; Z01 BC011043-01 United States ImNIH Intramural NIH HHS; Z01 SC006659-25 United States ImNIH Intramural NIH HHS |
| المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) 0 (Biomarkers, Tumor) 0 (Cell Cycle Proteins) 0 (GPNMB protein, human) 0 (Membrane Glycoproteins) 0 (Neoplasm Proteins) 0 (Oncogene Proteins, Fusion) 0 (PRCC protein, human) 0 (TFE3 protein, human) |
| تواريخ الأحداث: | Date Created: 20190503 Date Completed: 20200416 Latest Revision: 20240615 |
| رمز التحديث: | 20240615 |
| مُعرف محوري في PubMed: | PMC6679785 |
| DOI: | 10.1158/1541-7786.MCR-18-1235 |
| PMID: | 31043488 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3125 |
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| DOI: | 10.1158/1541-7786.MCR-18-1235 |