دورية أكاديمية
Enhanced immortalization, HUWE1 mutations and other biological drivers of breast invasive carcinoma in Black/African American patients.
| العنوان: | Enhanced immortalization, HUWE1 mutations and other biological drivers of breast invasive carcinoma in Black/African American patients. |
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| المؤلفون: | Andey T; Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster St, Worcester, MA 01608, USA., Attah MM; University of Massachusetts, Amherst, MA 01003, USA., Akwaaba-Reynolds NA; Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster St, Worcester, MA 01608, USA., Cheema S; Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster St, Worcester, MA 01608, USA., Parvin-Nejad S; Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster St, Worcester, MA 01608, USA., Acquaah-Mensah GK; Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, 19 Foster St, Worcester, MA 01608, USA. |
| المصدر: | Gene: X [Gene X] 2020 May 01; Vol. 5, pp. 100030. Date of Electronic Publication: 2020 May 01 (Print Publication: 2020). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101746496 Publication Model: eCollection Cited Medium: Internet ISSN: 2590-1583 (Electronic) Linking ISSN: 25901583 NLM ISO Abbreviation: Gene X Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam, Netherlands] : Elsevier B.V., [2019]- |
| مستخلص: | Black/African-American (B/AA) breast cancer patients tend to have more aggressive tumor biology compared to White/Caucasians. In this study, a variety of breast tumor molecular expression profiles of patients derived from the two racial groupings were investigated. Breast invasive carcinoma sample data (RNASeq version 2, Reverse Phase Protein Array, mutation, and miRSeq data) from the Cancer Genome Atlas were examined. The results affirm that B/AA patients are more likely than Caucasian patients to harbor the aggressive basal-like or the poor prognosis-associated HER2-enriched molecular subtypes of breast cancer. There is also a higher incidence of the triple-negative breast cancer (TNBC) among B/AA patients than the general population, a fact reflected in the mutation patterns of genes such as PIK3CA and TP53 . Furthermore, an immortalization signature gene set, is enriched in samples from B/AA patients. Among stage III patients, TERT, DRAP1, and PQBP1, all members of the immortalization gene signature set, are among master-regulators with increased activity in B/AA patients. Master-regulators driving differences in expression profiles between the two groups include immortalization markers, senescence markers, and immune response and redox gene products. Differences in expression, between B/AA and Caucasian patients, of RB1 , hsa-let-7a , E2F1 , c-MYC , TERT , and other biomolecules appear to cooperate to enhance entry into the S-phase of the cell cycle in B/AA patients. Higher expression of miR-221 , an oncomiR that facilitates entry into the cell cycle S-phase, is regulated by c-MYC , which is expressed more in breast cancer samples from B/AA patients. Furthermore, the cell migration- and invasion-promoting miRNA, miR-135b , has increased relative expression in B/AA patients. Knock down of the immortalization marker TERT inhibited triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) cell viability and decreased expression of TERT, MYC and WNT11. For those patients with available survival data, prognosis of stage II patients 50 years of age or younger at diagnosis, was distinctly poorer in B/AA patients. Also associated with this subset of B/AA patients are missense mutations in HUWE1 and PTEN expression loss. Relative to Caucasian non-responders to endocrine therapy, B/AA non-responders show suppressed expression of a signature gene set on which biological processes including signaling by interleukins , circadian clock , regulation of lipid metabolism by PPARα , FOXO-mediated transcription , and regulation of TP53 degradation are over-represented. Thus, we identify molecular expression patterns suggesting diminished response to oxidative stress, changes in regulation of tumor suppressors/facilitators, and enhanced immortalization in B/AA patients are likely important in defining the more aggressive molecular tumor phenotype reported in B/AA patients. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2020 The Author(s).) |
| References: | Cancer Epidemiol Biomarkers Prev. 2014 Feb;23(2):316-23. (PMID: 24296856) Eur J Pharm Sci. 2013 Oct 9;50(2):227-41. (PMID: 23892137) Oncogene. 2003 May 15;22(19):2972-83. (PMID: 12771949) Cancer Res. 2008 Feb 15;68(4):989-97. (PMID: 18281472) J Control Release. 2014 Jun 28;184:67-78. (PMID: 24727000) Oncogene. 2007 Sep 20;26(43):6269-79. (PMID: 17471242) Cell Stress Chaperones. 2005 Summer;10(2):86-103. (PMID: 16038406) PLoS One. 2014 Jan 16;9(1):e78644. (PMID: 24454679) Nucleic Acids Res. 2010 Jan;38(Database issue):D119-22. (PMID: 19786497) J Clin Invest. 2015 May;125(5):2109-22. (PMID: 25893605) Oncologist. 2013;18(2):123-33. (PMID: 23404817) J Clin Invest. 2016 Oct 3;126(10):4045-4060. (PMID: 27643433) Curr Probl Cancer. 2016 Mar - Aug;40(2-4):130-140. (PMID: 28340968) Nat Genet. 2016 Aug;48(8):838-47. (PMID: 27322546) Biostatistics. 2003 Apr;4(2):249-64. (PMID: 12925520) Lancet Oncol. 2014 Dec;15(13):e625-e634. (PMID: 25456381) Nature. 2009 Jul 2;460(7251):66-72. (PMID: 19571879) Oncotarget. 2016 Mar 8;7(10):11364-79. (PMID: 26689987) Cancer. 2007 May 1;109(9):1721-8. (PMID: 17387718) Epigenetics. 2015;10(12):1177-87. (PMID: 26680018) Molecules. 2014 May 30;19(6):7122-37. (PMID: 24886939) Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Oct;31(10):1316-21. (PMID: 26429530) Expert Rev Anticancer Ther. 2017 Jul;17(7):607-613. (PMID: 28597750) Int J Oncol. 2017 May;50(5):1567-1578. (PMID: 28393241) Cancers (Basel). 2017 Sep 30;9(10):. (PMID: 28974015) PLoS One. 2013 May 02;8(5):e63419. (PMID: 23658826) Oncologist. 2010;15(5):466-75. (PMID: 20427382) Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651) J Surg Res. 2007 Nov;143(1):109-18. (PMID: 17950079) Cancer Res. 2008 Sep 15;68(18):7493-501. (PMID: 18794137) Breast. 2015 Oct;24(5):642-8. (PMID: 26279132) Bioinformatics. 2016 Apr 1;32(7):1097-9. (PMID: 26607490) Sci Rep. 2017 Sep 18;7(1):11768. (PMID: 28924209) Biochem Biophys Res Commun. 2014 Feb 14;444(3):290-5. (PMID: 24342616) J Clin Oncol. 2009 Mar 10;27(8):1160-7. (PMID: 19204204) Breast. 2006 Feb;15(1):90-5. (PMID: 16473740) BMC Bioinformatics. 2011 Aug 04;12:323. (PMID: 21816040) Genes Chromosomes Cancer. 2013 Jul;52(7):595-609. (PMID: 23629941) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Bioinformatics. 2016 Jul 15;32(14):2233-5. (PMID: 27153652) J Clin Oncol. 2015 Nov 1;33(31):3621-7. (PMID: 26371147) Nat Methods. 2014 Jun;11(6):599-600. (PMID: 24874569) Nature. 2008 Oct 23;455(7216):1061-8. (PMID: 18772890) Oncotarget. 2016 Nov 8;7(45):72807-72818. (PMID: 27637080) Breast Cancer Res Treat. 2015 Aug;153(1):57-66. (PMID: 26223813) Cancer Genomics Proteomics. 2019 May-Jun;16(3):195-206. (PMID: 31018950) Surg Oncol Clin N Am. 2014 Jul;23(3):567-77. (PMID: 24882351) Int J Hyperthermia. 2004 Dec;20(8):835-49. (PMID: 15764345) |
| معلومات مُعتمدة: | P30 CA016672 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: ARACNe, Algorithm for the Reconstruction of Accurate Cellular Networks; African; B/AA, Black/African-American breast cancer patients; B/AA50, Black/African-American stage II breast invasive carcinoma patients diagnosed at age 50 years or younger; BrCA, breast invasive carcinoma; Breast invasive carcinoma; DE, differential expression; DM, differential mutation; EMT, Epithelial-Mesenchymal Transition; GSEA, Gene Set Enrichment Analysis; Immortalization; Molecular subtype; RMA, robust multi-array average; RPPA, Reverse Phase Protein Array; Race; TCGA, the Cancer Genome Atlas; TNBC, triple-negative breast cancer; TRN, Transcriptional Regulatory Network; Triple-negative breast cancer; VIPER, Virtual Inference of Protein activity by Enriched Regulon Analysis; W50, White stage II breast invasive carcinoma patients diagnosed at age 50 years or younger |
| تواريخ الأحداث: | Date Created: 20200619 Latest Revision: 20231103 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7286073 |
| DOI: | 10.1016/j.gene.2020.100030 |
| PMID: | 32550556 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2590-1583 |
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| DOI: | 10.1016/j.gene.2020.100030 |