Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation

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

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3 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalDMM Disease Models and Mechanisms
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2018

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All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • Cancer initiation
  • Differentiation
  • Inflammation
  • NKX3.1
  • Prostate cancer

Cite this

Le Magnen, C., Virk, R. K., Dutta, A., Kim, J. Y., Panja, S., Lopez-Bujanda, Z. A., ... Abate-Shen, C. (2018). Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation. DMM Disease Models and Mechanisms, 11(11). https://doi.org/10.1242/dmm.035139