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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2014 Volume 34 Issue 5

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
November-2014 Volume 34 Issue 5

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

Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells

  • Authors:
    • Yu Ren
    • Jianjian Zheng
    • Xuping Yao
    • Guobin Weng
    • Ling Wu
  • View Affiliations / Copyright

    Affiliations: Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo, Zhejiang 315000, P.R. China, Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Urologic Surgery, Ningbo Yinzhou People's Hospital, Zhejiang 315000, P.R. China, Department of Pediatric Rheumatology and Immunology, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315000, P.R. China
  • Pages: 1430-1438
    |
    Published online on: September 8, 2014
       https://doi.org/10.3892/ijmm.2014.1925
  • 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

Phosphodiesterase type 5 (PDE5) plays a key role in regulating the intracellular cyclic GMP (cGMP) concentration, which influences anti-proliferative and pro-apoptotic mechanisms in multiple carcinomas. PDE5 inhibitors, such as exisulind and its analogs have anticancer activities. In this study, we found that suppressing PDE5 gene expression by PDE5 siRNA inhibited cell proliferation and induced apoptosis in OS-RC-2 human renal cell carcinoma cells. These effects were enhanced by 8-Br-cGMP, a cell membrane permeable cGMP derivative, and were inhibited by KT5823, a protein kinase G (PKG) inhibitor, indicating that PKG was activated by intracellular cyclic GMP. In addition, there was a reduction in both the mRNA and protein expression of cyclin D1, while p21 protein expression was increased; the reduction in cyclin D1 expression was blocked by the proteasome inhibitor, MG132, or c-Jun N-terminal kinase (JNK) inhibitor; both β-catenin and JNK were phosphorylated by activated PKG. Furthermore, p21 protein expression was decreased in Sp1 siRNA transfected-cells treated with 8-Br-cGMP, indicating that p21 may be partly controlled by the PKG activation through Sp1. Furthermore, we found that PKG Iβ was responsible for the anticancer activities. Our findings indicate that the downregulation of PKG-activated genes, such as cyclin D1 partly accounts for the pro-apoptotic effects in PDE5 siRNA-transfected OS-RC-2 cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Rini BI, Rathmell WK and Godley P: Renal cell carcinoma. Curr Opin Oncol. 20:300–306. 2008. View Article : Google Scholar

2 

Escudier B: Chemo-immunotherapy in RCC: the end of a story. Lancet. 375:613–614. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Mulders PF, Brouwers AH, Hulsbergen-van der Kaa CA, et al: Guideline ‘Renal cell carcinoma’. Ned Tijdschr Geneeskd. 152:376–380. 2008.(In Dutch).

4 

Zhu B and Strada SJ: The novel functions of cGMP-specific phosphodiesterase 5 and its inhibitors in carcinoma cells and pulmonary/cardiovascular vessels. Curr Top Med Chem. 7:437–454. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Thompson WJ, Piazza GA, Li H, et al: Exisulind induction of apoptosis involves guanosine 3′,5′-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 60:3338–3342. 2000.PubMed/NCBI

6 

Piazza GA, Thompson WJ, Pamukcu R, et al: Exisulind, a novel proapoptotic drug, inhibits rat urinary bladder tumorigenesis. Cancer Res. 61:3961–3968. 2001.PubMed/NCBI

7 

Zhu B, Vemavarapu L, Thompson WJ and Strada SJ: Suppression of cyclic GMP-specific phosphodiesterase 5 promotes apoptosis and inhibits growth in HT29 cells. J Cell Biochem. 94:336–350. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Lim JT, Piazza GA, Han EK, et al: Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Biochem Pharmacol. 58:1097–1107. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Tinsley HN, Gary BD, Keeton AB, et al: Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G. Mol Cancer Ther. 8:3331–3340. 2009. View Article : Google Scholar

10 

Tinsley HN, Gary BD, Keeton AB, et al: Inhibition of PDE5 by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/beta-catenin-mediated transcription in human breast tumor cells. Cancer Prev Res (Phila). 4:1275–1284. 2011. View Article : Google Scholar

11 

Tetsu O and McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422–426. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Li H, Liu L, David ML, et al: Pro-apoptotic actions of exisulind and CP461 in SW480 colon tumor cells involve beta-catenin and cyclin D1 downregulation. Biochem Pharmacol. 64:1325–1336. 2002. View Article : Google Scholar : PubMed/NCBI

13 

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

14 

Deguchi A, Thompson WJ and Weinstein IB: Activation of protein kinase G is sufficient to induce apoptosis and inhibit cell migration in colon cancer cells. Cancer Res. 64:3966–3973. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Carlson B, Lahusen T, Singh S, et al: Downregulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res. 59:4634–4641. 1999.PubMed/NCBI

16 

Liu L, Li H, Underwood T, et al: Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells. J Pharmacol Exp Ther. 299:583–592. 2001.PubMed/NCBI

17 

Kwon IK, Wang R, Thangaraju M, et al: PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. Oncogene. 29:3423–3434. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Soh JW, Mao Y, Kim MG, et al: Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1. Clin Cancer Res. 6:4136–4141. 2000.PubMed/NCBI

19 

Hofmann F: The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 280:1–4. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Das A, Xi L and Kukreja RC: Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem. 283:29572–29585. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Peruzzi B and Bottaro DP: Beta-catenin signaling: linking renal cell carcinoma and polycystic kidney disease. Cell Cycle. 5:2839–2841. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Thompson MD and Monga SP: WNT/beta-catenin signaling in liver health and disease. Hepatology. 45:1298–1305. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Chesire DR and Isaacs WB: Beta-catenin signaling in prostate cancer: an early perspective. Endocr Relat Cancer. 10:537–560. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Stein U, Arlt F, Smith J, et al: Intervening in beta-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia. 13:131–144. 2011.PubMed/NCBI

25 

Li H, Pamukcu R and Thompson WJ: beta-Catenin signaling: therapeutic strategies in oncology. Cancer Biol Ther. 1:621–625. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Ueda M, Gemmill RM, West J, et al: Mutations of the beta-and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas. Br J Cancer. 85:64–68. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Tarmin L, Yin J, Harpaz N, et al: Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms. Cancer Res. 55:2035–2038. 1995.PubMed/NCBI

28 

Lewis A, Davis H, Deheragoda M, et al: The C-terminus of Apc does not influence intestinal adenoma development or progression. J Pathol. 226:73–83. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Whitehead CM, Earle KA, Fetter J, et al: Exisulind-induced apoptosis in a non-small cell lung cancer orthotopic lung tumor model augments docetaxel treatment and contributes to increased survival. Mol Cancer Ther. 2:479–488. 2003.PubMed/NCBI

30 

Saikawa Y, Kubota T, Otani Y, et al: Cyclin D1 antisense oligonucleotide inhibits cell growth stimulated by epidermal growth factor and induces apoptosis of gastric cancer cells. Jpn J Cancer Res. 92:1102–1109. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ren Y, Zheng J, Yao X, Weng G and Wu L: Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells. Int J Mol Med 34: 1430-1438, 2014.
APA
Ren, Y., Zheng, J., Yao, X., Weng, G., & Wu, L. (2014). Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells. International Journal of Molecular Medicine, 34, 1430-1438. https://doi.org/10.3892/ijmm.2014.1925
MLA
Ren, Y., Zheng, J., Yao, X., Weng, G., Wu, L."Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells". International Journal of Molecular Medicine 34.5 (2014): 1430-1438.
Chicago
Ren, Y., Zheng, J., Yao, X., Weng, G., Wu, L."Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells". International Journal of Molecular Medicine 34, no. 5 (2014): 1430-1438. https://doi.org/10.3892/ijmm.2014.1925
Copy and paste a formatted citation
x
Spandidos Publications style
Ren Y, Zheng J, Yao X, Weng G and Wu L: Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells. Int J Mol Med 34: 1430-1438, 2014.
APA
Ren, Y., Zheng, J., Yao, X., Weng, G., & Wu, L. (2014). Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells. International Journal of Molecular Medicine, 34, 1430-1438. https://doi.org/10.3892/ijmm.2014.1925
MLA
Ren, Y., Zheng, J., Yao, X., Weng, G., Wu, L."Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells". International Journal of Molecular Medicine 34.5 (2014): 1430-1438.
Chicago
Ren, Y., Zheng, J., Yao, X., Weng, G., Wu, L."Essential role of the cGMP/PKG signaling pathway in regulating the proliferation and survival of human renal carcinoma cells". International Journal of Molecular Medicine 34, no. 5 (2014): 1430-1438. https://doi.org/10.3892/ijmm.2014.1925
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