Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation
Although it is known that inflammation plays a critical role in prostate tumorigenesis, the underlying processes are not well understood. Based on analysis of genetically engineered mouse models combined with correlative analysis of expression profiling data from human prostate tumors, we demonstrat...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-11-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/11/11/dmm035139 |
| _version_ | 1819040728413634560 |
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| author | Clémentine Le Magnen Renu K. Virk Aditya Dutta Jaime Yeji Kim Sukanya Panja Zoila A. Lopez-Bujanda Andrea Califano Charles G. Drake Antonina Mitrofanova Cory Abate-Shen |
| author_facet | Clémentine Le Magnen Renu K. Virk Aditya Dutta Jaime Yeji Kim Sukanya Panja Zoila A. Lopez-Bujanda Andrea Califano Charles G. Drake Antonina Mitrofanova Cory Abate-Shen |
| author_sort | Clémentine Le Magnen |
| collection | DOAJ |
| description | Although it is known that inflammation plays a critical role in prostate tumorigenesis, the underlying processes are not well understood. Based on analysis of genetically engineered mouse models combined with correlative analysis of expression profiling data from human prostate tumors, we demonstrate a reciprocal relationship between inflammation and the status of the NKX3.1 homeobox gene associated with prostate cancer initiation. We find that cancer initiation in aged Nkx3.1 mutant mice correlates with enrichment of specific immune populations and increased expression of immunoregulatory genes. Furthermore, expression of these immunoregulatory genes is similarly increased in human prostate tumors having low levels of NKX3.1 expression. We further show that induction of prostatitis in Nkx3.1 mutant mice accelerates prostate cancer initiation, which is coincident with aberrant cellular plasticity and differentiation. Correspondingly, human prostate tumors having low levels of NKX3.1 have de-regulated expression of genes associated with these cellular processes. We propose that loss of function of NKX3.1 accelerates inflammation-driven prostate cancer initiation potentially via aberrant cellular plasticity and impairment of cellular differentiation. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-21T09:13:43Z |
| format | Article |
| id | doaj.art-1101e9bdeeee454f88d94a0d8d3d0928 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-21T09:13:43Z |
| publishDate | 2018-11-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-1101e9bdeeee454f88d94a0d8d3d09282022-12-21T19:09:11ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-11-01111110.1242/dmm.035139035139Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiationClémentine Le Magnen0Renu K. Virk1Aditya Dutta2Jaime Yeji Kim3Sukanya Panja4Zoila A. Lopez-Bujanda5Andrea Califano6Charles G. Drake7Antonina Mitrofanova8Cory Abate-Shen9 Departments of Medicine and Urology, Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Department of Pathology and Cell Biology, Columbia University Medical Center, NY 10032, USA Departments of Medicine and Urology, Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Department of Health Informatics, Rutgers School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ 07101, USA Graduate Program in Pathobiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Departments of Systems Biology and Biochemistry and Molecular Biophysics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Department of Medicine, Columbia Center for Translational Immunology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Department of Health Informatics, Rutgers School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ 07101, USA Departments of Urology, Medicine, Pathology & Cell Biology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA Although it is known that inflammation plays a critical role in prostate tumorigenesis, the underlying processes are not well understood. Based on analysis of genetically engineered mouse models combined with correlative analysis of expression profiling data from human prostate tumors, we demonstrate a reciprocal relationship between inflammation and the status of the NKX3.1 homeobox gene associated with prostate cancer initiation. We find that cancer initiation in aged Nkx3.1 mutant mice correlates with enrichment of specific immune populations and increased expression of immunoregulatory genes. Furthermore, expression of these immunoregulatory genes is similarly increased in human prostate tumors having low levels of NKX3.1 expression. We further show that induction of prostatitis in Nkx3.1 mutant mice accelerates prostate cancer initiation, which is coincident with aberrant cellular plasticity and differentiation. Correspondingly, human prostate tumors having low levels of NKX3.1 have de-regulated expression of genes associated with these cellular processes. We propose that loss of function of NKX3.1 accelerates inflammation-driven prostate cancer initiation potentially via aberrant cellular plasticity and impairment of cellular differentiation. This article has an associated First Person interview with the first author of the paper.http://dmm.biologists.org/content/11/11/dmm035139Prostate cancerCancer initiationNKX3.1InflammationDifferentiation |
| spellingShingle | Clémentine Le Magnen Renu K. Virk Aditya Dutta Jaime Yeji Kim Sukanya Panja Zoila A. Lopez-Bujanda Andrea Califano Charles G. Drake Antonina Mitrofanova Cory Abate-Shen Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation Disease Models & Mechanisms Prostate cancer Cancer initiation NKX3.1 Inflammation Differentiation |
| title | Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation |
| title_full | Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation |
| title_fullStr | Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation |
| title_full_unstemmed | Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation |
| title_short | Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation |
| title_sort | cooperation of loss of nkx3 1 and inflammation in prostate cancer initiation |
| topic | Prostate cancer Cancer initiation NKX3.1 Inflammation Differentiation |
| url | http://dmm.biologists.org/content/11/11/dmm035139 |
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