Expression of interleukin-6 is downregulated by 17-(allylamino)-17-demethoxygeldanamycin in human prostatic carcinoma cells
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Updated: Jun 28, 2026
Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor Microenvironment
Published on: November 23, 2017
Ke-hung Tsui1, Tsui-hsia Feng, Wen-chi Hsieh
1Department of Urology, Chang Gung Memory Hospital, Kwei-Shan, Tao-Yuan, Taiwan, China.
Aim:
Interleukin-6 (IL-6) is a pleiotropic cytokine that is associated with tumor metastasis and prostate cancer. We evaluated the mechanism and effect of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), a novel inhibitor of heat shock protein 90 (Hsp90), on the IL-6 gene expression in human prostatic carcinoma (PC-3) cells.
Methods:
Quantitative IL-6 and IL-6 receptor (IL-6R) expressions were assessed using RT-PCR. The deregulation of 17AAG and phorbol 12-myristate 13-acetate (PMA) on the IL-6 gene was determined by ELISA and transient gene expression assays using an IL-6 reporter vector.
Results:
Although the IL-6R is ubiquitously expressed by prostatic epithelium cells, the IL-6 expression is only found in advanced prostatic carcinoma cells, such as PC-3 and DU145. Further studies using RT-PCR indicated that 17AAG downregulated the gene expression of IL-6. ELISA and the transient gene expression assay revealed that 17AAG blocked the stimulation of PMA of IL-6 gene expression in PC-3 cells. The PMA-induced IL-6 gene expression is dependent on the NF-kappaB response element. However, the effect of 17AAG appears to be mediated via a region located at -149 to +8 bp upstream of the transcriptional starting site of the IL-6 gene, and might not be through the NF-kappaB signaling pathway.
Conclusion:
The present study reveals that IL-6 is transcriptionally downregulated in human prostatic carcinoma cells in response to 17AAG. This result suggests the presence of a novel Hsp90 mediation pathway that is involved in the deregulation on the transcription of the human IL-6 gene in human prostate cancer.
Insights
17-(allylamino)-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, downregulates interleukin-6 (IL-6) gene expression in prostate cancer cells. This suggests a novel Hsp90 pathway involved in regulating IL-6 transcription in prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Interleukin-6 (IL-6) is a cytokine linked to tumor metastasis and prostate cancer progression.
- Heat shock protein 90 (Hsp90) is a molecular chaperone implicated in cancer cell survival and proliferation.
Purpose of the Study:
- To investigate the mechanism and effect of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, on IL-6 gene expression in human prostate cancer cells (PC-3).
Main Methods:
- Quantitative assessment of IL-6 and IL-6 receptor (IL-6R) expression using RT-PCR.
- ELISA and transient gene expression assays to determine the effect of 17AAG and phorbol 12-myristate 13-acetate (PMA) on IL-6 gene expression.
- Analysis of the IL-6 gene promoter region and potential signaling pathways (NF-kappaB).
Main Results:
- IL-6 expression is specific to advanced prostate cancer cells (PC-3, DU145), while IL-6R is widely expressed.
- 17AAG significantly downregulated IL-6 gene expression in PC-3 cells.
- 17AAG inhibited PMA-induced IL-6 gene expression, suggesting a mechanism independent of the NF-kappaB signaling pathway but involving a specific region of the IL-6 gene promoter.
Conclusions:
- 17AAG transcriptionally downregulates IL-6 in human prostate cancer cells.
- A novel Hsp90-mediated pathway may be involved in regulating IL-6 gene transcription in prostate cancer.
