STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells
Inflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulate...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/7/1579 |
| _version_ | 1797539613120659456 |
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| author | Nicklas Pihlstrøm Yang Jin Zeynep Nenseth Omer F. Kuzu Fahri Saatcioglu |
| author_facet | Nicklas Pihlstrøm Yang Jin Zeynep Nenseth Omer F. Kuzu Fahri Saatcioglu |
| author_sort | Nicklas Pihlstrøm |
| collection | DOAJ |
| description | Inflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulated gene, as well as a key regulator of PCa growth and survival. STAMP2 is also regulated by, and participates in, inflammatory signaling in other tissues and pathologies. Here, we show that the proinflammatory cytokines interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β) significantly increase and strongly synergize in promoting STAMP2 expression in PCa cells. The two cytokines increase androgen-induced STAMP2 expression, but not expression of other known androgen target genes, suggesting a unique interplay of androgens and cytokines in regulating STAMP2 expression. Interestingly, STAMP2 knockdown significantly increased the ability of IL-6 and IL-1β to inhibit PCa cell growth in vitro. These results suggest that STAMP2 may represent a unique node through which inflammatory events mediate their effects on PCa growth and survival. |
| first_indexed | 2024-03-10T12:47:21Z |
| format | Article |
| id | doaj.art-5d1baab237734055ad24f02338dc1831 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:47:21Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5d1baab237734055ad24f02338dc18312023-11-21T13:20:14ZengMDPI AGCancers2072-66942021-03-01137157910.3390/cancers13071579STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer CellsNicklas Pihlstrøm0Yang Jin1Zeynep Nenseth2Omer F. Kuzu3Fahri Saatcioglu4Department of Biosciences, University of Oslo, 0315 Oslo, NorwayDepartment of Biosciences, University of Oslo, 0315 Oslo, NorwayDepartment of Biosciences, University of Oslo, 0315 Oslo, NorwayDepartment of Biosciences, University of Oslo, 0315 Oslo, NorwayDepartment of Biosciences, University of Oslo, 0315 Oslo, NorwayInflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulated gene, as well as a key regulator of PCa growth and survival. STAMP2 is also regulated by, and participates in, inflammatory signaling in other tissues and pathologies. Here, we show that the proinflammatory cytokines interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β) significantly increase and strongly synergize in promoting STAMP2 expression in PCa cells. The two cytokines increase androgen-induced STAMP2 expression, but not expression of other known androgen target genes, suggesting a unique interplay of androgens and cytokines in regulating STAMP2 expression. Interestingly, STAMP2 knockdown significantly increased the ability of IL-6 and IL-1β to inhibit PCa cell growth in vitro. These results suggest that STAMP2 may represent a unique node through which inflammatory events mediate their effects on PCa growth and survival.https://www.mdpi.com/2072-6694/13/7/1579STAMP2STEAP4cytokinesIL-6IL-1βprostate cancer |
| spellingShingle | Nicklas Pihlstrøm Yang Jin Zeynep Nenseth Omer F. Kuzu Fahri Saatcioglu STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells Cancers STAMP2 STEAP4 cytokines IL-6 IL-1β prostate cancer |
| title | STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells |
| title_full | STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells |
| title_fullStr | STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells |
| title_full_unstemmed | STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells |
| title_short | STAMP2 Expression Mediated by Cytokines Attenuates Their Growth-Limiting Effects in Prostate Cancer Cells |
| title_sort | stamp2 expression mediated by cytokines attenuates their growth limiting effects in prostate cancer cells |
| topic | STAMP2 STEAP4 cytokines IL-6 IL-1β prostate cancer |
| url | https://www.mdpi.com/2072-6694/13/7/1579 |
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