Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
February-2019 Volume 41 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2019 Volume 41 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells

  • Authors:
    • D. Herrera
    • O. Orellana‑Serradell
    • P. Villar
    • M. J. Torres
    • R. Paciucci
    • E. A. Castellón
    • H. R. Contreras
  • View Affiliations / Copyright

    Affiliations: Department of Basic and Clinic Oncology, Faculty of Medicine, University of Chile, 8380453 Santiago, Chile, Biomedical Research Group of Urology, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
  • Pages: 1275-1283
    |
    Published online on: November 26, 2018
       https://doi.org/10.3892/or.2018.6885
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Prostate cancer (PCa) is the second most common type of male malignancy worldwide. The transcription factor zinc finger E‑box binding homeobox 1 (ZEB1) is associated with epithelial‑mesenchymal transition and is also involved in regulation of androgen receptor (AR) expression, the main ligands of which are testosterone and dihydrotestosterone (DHT). These androgens are synthesized through the steroidogenic pathway within the prostate, and their synthesis is altered in PCa. The present study aimed to determine the ZEB1‑induced alterations in androgen synthesis and AR expression in the DU145 PCa cell line. Reverse transcription‑quantitative polymerase chain reaction, western blotting and immunocytochemistry were used to determine the mRNA and protein expression levels, and cellular localization of steroidogenic pathway enzymes in the DU145 cell line in response to ZEB1 silencing. Furthermore, the concentrations of testosterone and DHT were detected in cell culture medium using ELISA. ZEB1‑silenced cells exhibited an increase in testosterone and DHT production, an increase in AR expression and an alteration in the steroidogenic pathway. In particular, steroidogenic acute regulatory protein and 5α‑reductase 2 expression levels were decreased, whereas cytochrome P450 family 17 subfamily A member 1, 5α‑reductase 1, aldo‑keto reductase family 1 member D1 and aldo‑keto reductase family 1 member C2 expression levels were increased. In conclusion, the present study provided novel information regarding the regulation of intratumoral androgen production in PCa, which is relevant for the progression of the disease to a castration‑resistant form.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Anantharaman A and Frieddlaner TW: Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: A review. Urol Oncol. 34:356–367. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Lonergan PE and Tindall DJ: Androgen receptor signaling in prostate cancer development and progression. J Carcinog. 10:202011. View Article : Google Scholar : PubMed/NCBI

4 

Chandrasekar T, Yang JC, Gao AC and Evans CP: Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 4:365–380. 2015.PubMed/NCBI

5 

Mitsiades N, Sung C, Schultz N, Danila DC, He B, Eedunuri VK, Fleisher M, Sander C, Sawyers CL and Scher HI: Distinct patterns of dysregulated expression of enzymes involved in androgen synthesis and metabolism in metastatic prostate cancer tumors. Cancer Res. 72:6142–6152. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Banerjee P, Banerjee S, Brown T and Zirkin B: Androgen action in prostate function and disease. Am J Clin Exp Urol. 6:62–77. 2018.PubMed/NCBI

7 

Sun Y, Wang BE, Leong KG, Yue P, Li L, Jhunjhunwala S, Chen D, Seo K, Modrusan Z, Gao WQ, et al: Androgen deprivation causes epithelial-mesenchymal transition in the prostate: Implications for androgen-deprivation therapy. Cancer Res. 72:527–536. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Anose BM and Sanders MM: Androgen receptor regulates transcription of the ZEB1 transcription factor. Int J Endocrinol. 2011:9039182011. View Article : Google Scholar : PubMed/NCBI

9 

Orellana-Serradell O, Herrera D, Castellon E and Contreras HR: The transcription factor ZEB1 promotes an aggressive phenotype in prostate cancer cell lines. Asian J Androl. 20:294–299. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Payne AH and Hales DB: Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev. 25:947–970. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Mostaghel EA: Steroid hormone synthetic pathways in prostate cancer. Transl Androl Urol. 2:212–227. 2013.PubMed/NCBI

13 

Chen M and Penning TM: 5β-Reduced steroids and human Δ4-3-ketosteroid 5β-reductase (AKR1D1). Steroids. 83:17–26. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Zeng CM, Chang LL, Ying MD, Cao J, He QJ, Zhu H and Yang B: Aldo-keto reductase AKR1C1-AKR1C4: Functions, regulation, and intervention for anti-cancer therapy. Front Pharmacol. 8:1192017. View Article : Google Scholar : PubMed/NCBI

15 

Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD and Nelson PS: Maintenance of intratumoral androgens in metastatic prostate cancer: A mechanism for castration-resistant tumor growth. Cancer Res. 68:4447–4454. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR and Penning TM: Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1 C2) and androgen metabolism in prostate cells. Endocrinology. 144:2922–2932. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Basu S and Tindall DJ: Androgen action in prostate cancer. Horm Cancer. 1:223–228. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, et al: Integrative genomic profiling of human prostate cancer. Cancer Cell. 18:11–22. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Zhang A, Zhang J, Plymate S and Mostaghel EA: Classical and non-classical roles for pre-receptor control of DHT metabolism in prostate cancer progression. Horm Cancer. 7:104–113. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Huang KH, Chiou SH, Chow KC, Lin TY, Chang HW, Chiang IP and Lee MC: Overexpression of aldo-keto reductase 1C2 is associated with disease progression in patients with prostatic cancer. Histopathology. 57:384–394. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Ji Q, Chang L, VanDenBerg D, Stanczyk FZ and Stolz A: Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. Prostate. 54:275–289. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Kobayashi T, Inoue T, Kamba T and Ogawa O: Experimental evidence of persistent androgen-receptor-dependency in castration-resistant prostate cancer. Int J Mol Sci. 14:15615–15635. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Lubik A, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, et al: Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment. Int J Cancer. 140:358–369. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Audet-Walsh É, Yee T, Tam IS and Giguère V: Inverse regulation of DHT synthesis enzymes 5α-reductase types 1 and 2 by the androgen receptor in prostate cancer. Endocrinology. 158:1015–1021. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, Ettinger SL, Gleave ME and Nelson CC: Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 68:6407–6415. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Herrera D, Orellana‑Serradell O, Villar P, Torres MJ, Paciucci R, Castellón EA and Contreras HR: Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells. Oncol Rep 41: 1275-1283, 2019.
APA
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M.J., Paciucci, R., Castellón, E.A., & Contreras, H.R. (2019). Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells. Oncology Reports, 41, 1275-1283. https://doi.org/10.3892/or.2018.6885
MLA
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M. J., Paciucci, R., Castellón, E. A., Contreras, H. R."Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells". Oncology Reports 41.2 (2019): 1275-1283.
Chicago
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M. J., Paciucci, R., Castellón, E. A., Contreras, H. R."Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells". Oncology Reports 41, no. 2 (2019): 1275-1283. https://doi.org/10.3892/or.2018.6885
Copy and paste a formatted citation
x
Spandidos Publications style
Herrera D, Orellana‑Serradell O, Villar P, Torres MJ, Paciucci R, Castellón EA and Contreras HR: Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells. Oncol Rep 41: 1275-1283, 2019.
APA
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M.J., Paciucci, R., Castellón, E.A., & Contreras, H.R. (2019). Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells. Oncology Reports, 41, 1275-1283. https://doi.org/10.3892/or.2018.6885
MLA
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M. J., Paciucci, R., Castellón, E. A., Contreras, H. R."Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells". Oncology Reports 41.2 (2019): 1275-1283.
Chicago
Herrera, D., Orellana‑Serradell, O., Villar, P., Torres, M. J., Paciucci, R., Castellón, E. A., Contreras, H. R."Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells". Oncology Reports 41, no. 2 (2019): 1275-1283. https://doi.org/10.3892/or.2018.6885
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team