Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation
| Autor: | Andrea Califano, Charles G. Drake, Renu K. Virk, Zoila A. Lopez-Bujanda, Antonina Mitrofanova, Sukanya Panja, Aditya Dutta, Cory Abate-Shen, Clémentine Le Magnen, Jaime Yeji Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Carcinogenesis Cell Plasticity Medicine (miscellaneous) lcsh:Medicine medicine.disease_cause urologic and male genital diseases Prostate cancer Immunology and Microbiology (miscellaneous) Prostate NKX3.1 Cell Differentiation 3. Good health Prostatitis Gene Expression Regulation Neoplastic medicine.anatomical_structure Phenotype Differentiation medicine.symptom lcsh:RB1-214 Research Article Neuroscience (miscellaneous) Inflammation Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine lcsh:Pathology Animals Humans Cell Lineage Cancer initiation Loss function Homeodomain Proteins lcsh:R Cancer Prostatic Neoplasms medicine.disease Mice Mutant Strains Gene expression profiling Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Chronic Disease Cancer research Transcription Factors |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 11, Iss 11 (2018) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | 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. Summary: Chronic inflammation collaborates with loss of function of the prostate-specific tumor-suppressor NKX3.1 to promote prostate cancer initiation, increase cellular plasticity and impair cellular differentiation. |
| Databáze: | OpenAIRE |
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