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Knockdown of STEAP1 inhibits cell growth and induces apoptosis in LNCaP prostate cancer cells counteracting the effect of androgens

Abstract

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed in numerous types of tumors, especially in prostate cancer. STEAP1 is located in the plasma membrane of epithelial cells and may play an important role in inter- and intracellular communication. Several studies suggest STEAP1 as a potential biomarker and an immunotherapeutic target for prostate cancer. However, the role of STEAP1 in cell proliferation and apoptosis remains unclear. Therefore, the role of STEAP1 in prostate cancer cells proliferation and apoptosis was determined by inducing STEAP1 gene knockdown in LNCaP cells. In addition, the effect of DHT on the proliferation of LNCaP cells knocked down for STEAP1 gene was evaluated. Our results demonstrated that silencing the STEAP1 gene reduces LNCaP cell viability and proliferation, while inducing apoptosis. In addition, we showed that the cellular and molecular effects of STEAP1 gene knockdown may be independent of DHT treatment, and blocking STEAP1 may reveal to be an appropriate strategy to activate apoptosis in cancer cells, as well as to prevent the proliferative and anti-apoptotic effects of DHT in prostate cancer.

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Acknowledgements

Thanks are due to Santander Totta Bank for the research grant to Inês M Gomes and Foundation for Science and Technology (FCT) for the PhD scholarships to Sandra Rocha (SFRH/BD/115693/2016) and Carlos Gaspar (SFRH/BDE/112920/2015).

Funding

This work is supported by FEDER funds through the POCI—COMPETE 2020—Operational Programme Competitiveness and Internationalisation in Axis I—Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT—Foundation for Science and Technology (Project UID/Multi/00709).

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IMG and SMR performed the collection, wrote and edited the manuscript and also contributed to the analysis and interpretation of data; CG and MIA performed the collection and contributed to the data analysis; CRS and SS designed the conceptual study, contributed to the analysis and interpretation of data and also involved in the critical reading of the manuscript; and CJM designed the conceptual study, contributed to the analysis and interpretation of data, involved in the critical reading of the manuscript and also approval of the final manuscript.

Corresponding author

Correspondence to Cláudio Jorge Maia.

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The authors declare that they have no conflicts of interest with the contents of this article.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Gomes, I.M., Rocha, S.M., Gaspar, C. et al. Knockdown of STEAP1 inhibits cell growth and induces apoptosis in LNCaP prostate cancer cells counteracting the effect of androgens. Med Oncol 35, 40 (2018). https://doi.org/10.1007/s12032-018-1100-0

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  • DOI: https://doi.org/10.1007/s12032-018-1100-0

Keywords

  • STEAP1
  • Prostate cancer
  • siRNA
  • Apoptosis
  • Proliferation