دورية أكاديمية
أعرض في EDS

In vivo genome-editing screen identifies tumor suppressor genes that cooperate with Trp53 loss during mammary tumorigenesis.

التفاصيل البيبلوغرافية
العنوان: In vivo genome-editing screen identifies tumor suppressor genes that cooperate with Trp53 loss during mammary tumorigenesis.
المؤلفون: Heitink L; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia., Whittle JR; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Vaillant F; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia., Capaldo BD; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia., Dekkers JF; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Dawson CA; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Milevskiy MJG; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia., Surgenor E; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Tsai M; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Chen HR; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Christie M; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Pathology, The Royal Melbourne Hospital, Parkville, Australia., Chen Y; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Smyth GK; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; School of Mathematics and Statistics, The University of Melbourne, Parkville, Australia., Herold MJ; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Strasser A; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Lindeman GJ; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Visvader JE; ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Australia.
المصدر: Molecular oncology [Mol Oncol] 2022 Mar; Vol. 16 (5), pp. 1119-1131. Date of Electronic Publication: 2022 Jan 26.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101308230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-0261 (Electronic) Linking ISSN: 15747891 NLM ISO Abbreviation: Mol Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : Hoboken, New Jersey : John Wiley & Sons, Inc.
Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: CRISPR-Cas Systems*/genetics , Gene Editing*, Animals ; Cell Transformation, Neoplastic/genetics ; Genes, Tumor Suppressor ; Humans ; Mice ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
مستخلص: Breast cancer is a heterogeneous disease that comprises multiple histological and molecular subtypes. To gain insight into mutations that drive breast tumorigenesis, we describe a pipeline for the identification and validation of tumor suppressor genes. Based on an in vivo genome-wide CRISPR/Cas9 screen in Trp53 +/- heterozygous mice, we identified tumor suppressor genes that included the scaffold protein Axin1, the protein kinase A regulatory subunit gene Prkar1a, as well as the proof-of-concept genes Pten, Nf1, and Trp53 itself. Ex vivo editing of primary mammary epithelial organoids was performed to further interrogate the roles of Axin1 and Prkar1a. Increased proliferation and profound changes in mammary organoid morphology were observed for Axin1/Trp53 and Prkar1a/Trp53 double mutants compared to Pten/Trp53 double mutants. Furthermore, direct in vivo genome editing via intraductal injection of lentiviruses engineered to express dual short-guide RNAs revealed that mutagenesis of Trp53 and either Prkar1a, Axin1, or Pten markedly accelerated tumor development compared to Trp53-only mutants. This proof-of-principle study highlights the application of in vivo CRISPR/Cas9 editing for uncovering cooperativity between defects in tumor suppressor genes that elicit mammary tumorigenesis.
(© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
References: Hum Mol Genet. 2010 Apr 15;19(8):1387-98. (PMID: 20080939)
PLoS One. 2013 May 14;8(5):e62113. (PMID: 23690930)
Nat Biotechnol. 2014 Mar;32(3):267-73. (PMID: 24535568)
Gastroenterology. 2012 Dec;143(6):1650-9. (PMID: 22960659)
Cell. 2012 Jun 8;149(6):1245-56. (PMID: 22682247)
Nat Commun. 2021 May 24;12(1):3055. (PMID: 34031411)
Nat Med. 2009 Aug;15(8):907-13. (PMID: 19648928)
Oncogene. 2000 Feb 21;19(8):1052-8. (PMID: 10713689)
Dev Cell. 2007 Aug;13(2):268-82. (PMID: 17681137)
Nucleic Acids Res. 2019 May 7;47(8):e47. (PMID: 30783653)
Nat Cell Biol. 2009 Sep;11(9):1128-34. (PMID: 19731416)
Dev Cell. 2020 Dec 7;55(5):544-557.e6. (PMID: 33120014)
Cell. 1997 Jul 11;90(1):181-92. (PMID: 9230313)
Am J Pathol. 2000 Dec;157(6):2151-9. (PMID: 11106587)
Cell. 2015 Mar 12;160(6):1246-60. (PMID: 25748654)
Cell Rep. 2016 Sep 20;16(12):3146-3156. (PMID: 27653681)
Science. 1990 Nov 30;250(4985):1233-8. (PMID: 1978757)
Nat Genet. 2000 Mar;24(3):245-50. (PMID: 10700176)
Nat Genet. 2007 Jun;39(6):759-69. (PMID: 17468756)
Cell Rep. 2015 Mar 3;10(8):1422-32. (PMID: 25732831)
Breast Cancer Res. 2009;11(5):R66. (PMID: 19735549)
Nature. 2011 Jan 20;469(7330):314-22. (PMID: 21248838)
Cell. 2006 Sep 8;126(5):955-68. (PMID: 16959574)
Science. 2014 Jan 3;343(6166):84-87. (PMID: 24336571)
Nature. 2016 May 25;534(7605):55-62. (PMID: 27251275)
Nature. 2012 Oct 4;490(7418):61-70. (PMID: 23000897)
J Natl Cancer Inst. 2020 May 1;112(5):540-544. (PMID: 31589320)
Nature. 2016 May 02;534(7605):47-54. (PMID: 27135926)
Nat Protoc. 2019 Jun;14(6):1756-1771. (PMID: 31053799)
J Hepatol. 2018 Jun;68(6):1203-1213. (PMID: 29525529)
Biol Chem. 2010 Feb-Mar;391(2-3):171-180. (PMID: 20128690)
Nature. 2006 Feb 23;439(7079):993-7. (PMID: 16395311)
Sci Rep. 2016 Dec 16;6:38968. (PMID: 27982060)
Cancer Cell. 2019 Apr 15;35(4):618-632.e6. (PMID: 30930118)
Science. 2020 Mar 27;367(6485):1468-1473. (PMID: 32029688)
Development. 2017 Mar 15;144(6):1065-1071. (PMID: 27993977)
Cell. 2016 Jan 14;164(1-2):293-309. (PMID: 26771497)
Genome Biol. 2010;11(3):R25. (PMID: 20196867)
Nature. 2017 Jul 27;547(7664):413-418. (PMID: 28723893)
F1000Res. 2016 Jun 20;5:1438. (PMID: 27508061)
BMC Cancer. 2015 Apr 03;15:221. (PMID: 25879659)
Nature. 2012 Apr 04;486(7403):395-9. (PMID: 22495314)
Nature. 2006 Jan 5;439(7072):84-8. (PMID: 16397499)
Oncogene. 2015 Feb 26;34(9):1160-73. (PMID: 24662820)
Cell. 2015 Oct 8;163(2):506-19. (PMID: 26451490)
Nature. 2012 Apr 18;486(7403):346-52. (PMID: 22522925)
فهرسة مساهمة: Keywords: CRISPR/Cas9; Prkar1a; Trp53; axin1; breast cancer; intraductal; mammary organoids
المشرفين على المادة: 0 (Tumor Suppressor Protein p53)
تواريخ الأحداث: Date Created: 20220109 Date Completed: 20220408 Latest Revision: 20220408
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8895454
DOI: 10.1002/1878-0261.13179
PMID: 35000262
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-0261
DOI:10.1002/1878-0261.13179