Research Article Open Access
Volume 2 | Issue 4 | DOI: https://doi.org/10.33696/Signaling.2.058

Chronic IL-1 Exposed AR+ PCa Cell Lines Show Conserved Loss of IL-1 Sensitivity and Evolve Both Conserved and Unique Differential Gene Expression Profiles

  • 1Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA
  • 2McDermott Center of Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX 75390,USA
  • 3Department of Bioinformatics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • 4Department of Population and Data Sciences, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
+ Affiliations - Affiliations

Corresponding Author

Nikki A. Delk, nikki.delk@utdallas.edu

Received Date: August 26, 2021

Accepted Date: October 29, 2021


Introduction: Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells. However, acute inflammation is primarily anti-tumorigenic, while chronic inflammation is pro-tumorigenic. Thus, using the LNCaP PCa cell line as model, we found that PCa cells can evolve insensitivity to chronic IL-1 exposure, restoring AR and AR activity and acquiring castration resistance. In this paper we expanded our chronic IL-1 model to include the MDA-PCa-2b PCa cell line to investigate the response to acute versus chronic IL-1 exposure and to compare the gene expression patterns that evolve in the LNCaP and MDA-PCa-2b cells chronically exposed to IL-1.

Methods: We chronically exposed MDA-PCa-2b cells to IL-1a or IL-1ß for several months to establish sublines. Once established, we determined subline sensitivity to exogenous IL-1 using cell viability assay, RT-qPCR and western blot. RNA sequencing was performed for parental and subline cells and over representation analysis (ORA) for geneset enrichment of biological process/pathway was performed.

Results: MDA-PCa-2b cells repress AR and AR activity in response to acute IL-1 exposure and evolve insensitivity to chronic IL-1 exposure. While cell biological and molecular response to acute IL-1 signaling is primarily conserved in LNCaP and MDA-PCa-2b cells, including upregulation of NF-κB signaling and downregulation of cell proliferation, the LNCaP and MDA-PCa-2b cells evolve conserved and unique molecular responses to chronic IL-1 signaling that may promote or support tumor progression.

Conclusions: Our chronic IL-1 subline models can be used to identify underlying molecular mechanisms that mediate IL-1-induced PCa progression.


Chronic inflammation, Interleukin-1, IL-1, Prostate cancer, Gene expression

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