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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2017 Volume 13 Issue 6

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
June-2017 Volume 13 Issue 6

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

Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4

  • Authors:
    • Hyun‑Jung Park
    • Seung‑Hyun Kim
    • Dong‑Oh Moon
  • View Affiliations / Copyright

    Affiliations: Department of Biology Education, Daegu University, Gyeongsan, Gyeongsangbuk-do 38453, Republic of Korea
  • Pages: 4357-4363
    |
    Published online on: April 7, 2017
       https://doi.org/10.3892/ol.2017.6009
  • 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

Breast cancer remains the second largest cause of mortality in women with cancer and does not respond well to conventional therapies. Regulator of G‑protein signaling 4 (RGS4) is a GTPase‑activating protein of the heterotrimeric Gq and Gi proteins. Altered levels of RGS4 are reportedly linked with several human diseases, including cancer. The present study investigated whether overexpression of RGS4 inhibited the growth of human breast cancer cells. Protein expression was investigated by western blot analysis. Cell viability and apoptosis were analyzed by MTT assay and flow cytometric analysis, respectively. Cell cycle analysis was performed using propidium iodide staining in order to examine the anti‑proliferative function of increased RGS4 levels. Next, changes in the expression levels of G2/M cell cycle‑related proteins were examined. Overexpression of RGS4 led to the upregulation of phosphorylayed (p)‑Ser216 cell division cycle (Cdc)25C and p‑Tyr15 Cdc2. Importantly, MG132‑induced proteasome blockade prevented degradation of RGS4. Suppression of proliferation was associated with G2/M‑phase cell cycle arrest. Furthermore, enhanced endogenous RGS4 protein levels significantly inhibited breast cancer cell growth, which was reversed by a pharmacological inhibitor of RGS4. Taken together, these results suggest that overexpression of RGS4 in human breast cancer cells by molecular means may offer a potential therapeutic approach.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Feuer EJ, Wun LM, Boring CC, Flanders WD, Timmel MJ and Tong T: The life time risk of developing breast cancer. J Natl Cancer Inst. 85:892–897. 1993. View Article : Google Scholar : PubMed/NCBI

2 

Condeelis J, Singer RH and Segall JE: The great escape: When cancer cells hijack the genes for chemotaxis and motility. Annu Rev Cell Dev Biol. 21:695–718. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Dorsam RT and Gutkind JS: G-protein-coupled receptors and cancer. Nat Rev Cancer. 7:79–94. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Feigin ME: Harnessing the genome for characterization of G-protein coupled receptors in cancer pathogenesis. FEBS J. 280:4729–4738. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Gilman AG: G proteins: Transducers of receptor-generated signals. Annu Rev Biochem. 56:615–649. 1987. View Article : Google Scholar : PubMed/NCBI

6 

Ross EM and Wilkie TM: GTPase-activating proteins for heterotrimeric G proteins: Regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem. 69:795–827. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Hao J, Michalek C, Zhang W, Zhu M, Xu X and Mende U: Regulation of cardiomyocyte signaling by RGS proteins: Differential selectivity towards G proteins and susceptibility to regulation. J Mol Cell Cardiol. 41:51–61. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Mittmann C, Chung CH, Höppner G, Michalek C, Nose M, Schüler C, Schuh A, Eschenhagen T, Weil J, Pieske B, et al: Expression of ten RGS proteins in human myocardium: Functional characterization of an upregulation of RGS4 in heart failure. Cardiovasc Res. 55:778–786. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Owen VJ, Burton PB, Mullen AJ, Birks EJ, Barton P and Yacoub MH: Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure. Eur Heart J. 22:1015–1020. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Xie Y, Wolff DW, Wei T, Wang B, Deng C, Kirui JK, Jiang H, Qin J, Abel PW and Tu Y: Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4. Cancer Res. 69:5743–5751. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Lee PC, Sowa ME, Gygi SP and Harper JW: Alternative ubiquitin activation/conjugation cascades interact with N-end rule ubiquitin ligases to control degradation of RGS proteins. Mol Cell. 43:392–405. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Davydov IV and Varshavsky A: RGS4 is arginylated and degraded by the N-end rule pathway in vitro. J Biol Chem. 275:22931–22941. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Popov S, Yu K, Kozasa T and Wilkie TM: The regulators of G protein signaling (RGS) domains of RGS4, RGS10, and GAIP retain GTPase activating protein activity in vitro. Proc Natl Acad Sci USA. 94:7216–7220. 1997. View Article : Google Scholar : PubMed/NCBI

14 

Hubbard KB and Hepler JR: Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. Cell Signal. 18:135–150. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Tirziu D and Simons M: Endothelium-driven myocardial growth or nitric oxide at the crossroads. Trends Cardiovasc Med. 18:299–305. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Van Berlo JH, Maillet M and Molkentin JD: Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest. 123:37–45. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Dupré DJ, Robitaille M, Rebois RV and Hébert TE: The role of Gbetagamma subunits in the organization, assembly, and function of GPCR signaling complexes. Annu Rev Pharmacol Toxicol. 49:31–56. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Levitt P, Ebert P, Mirnics K, Nimgaonkar VL and Lewis DA: Making the case for a candidate vulnerability gene in schizophrenia: Convergent evidence for regulator of G-protein signaling 4 (RGS4). Biol Psychiatry. 60:534–537. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Tekumalla PK, Calon F, Rahman Z, Birdi S, Rajput AH, Hornykiewicz O, Di Paolo T, Bédard PJ and Nestler EJ: Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease. Biol Psychiatry. 50:813–816. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA and Casey PJ: The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci USA. 103:8173–8178. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Riccardi C and Nicoletti I: Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc. 1:1458–1461. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Wang TH, Wang HS and Soong YK: Paclitaxel-induced cell death: Where the cell cycle and apoptosis come together. Cancer. 88:2619–2628. 2000. View Article : Google Scholar : PubMed/NCBI

23 

O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, et al: mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 66:1500–1508. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Bodenstein J, Sunahara RK and Neubig RR: N-terminal residues control proteasomal degradation of RGS2, RGS4 and RGS5 in human embryonic kidney 293 cells. Mol Pharmacol. 71:1040–1050. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Krumins AM, Barker SA, Huang C, Sunahara RK, Yu K, Wilkie TM, Gold SJ and Mumby SM: Differentially regulated expression of endogenous RGS4 and RGS7. J Biol Chem. 279:2593–2599. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H and Elledge SJ: Conservation of the Chk1 checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25. Science. 277:1497–1501. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS and Piwnica-Worms H: Mitotic and G2 checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science. 277:1501–1505. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Kumagai A and Dunphy WG: Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25. Genes Dev. 13:1067–1072. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Dumesic PA, Scholl FA, Barragan DI and Khavari PA: Erk1/2 MAP kinases are required for epidermal G2/M progression. J Cell Biol. 185:409–422. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Palmer A, Gavin AC and Nebreda AR: A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1. EMBO J. 17:5037–5047. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Chambard JC, Lefloch R, Pouysségur J and Lenormand P: ERK implication in cell cycle regulation. Biochim Biophys Acta. 1773:1299–1310. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Chen L and Madura K: Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res. 65:5599–5606. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Park HJ, Kim SH and Moon DO: Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4. Oncol Lett 13: 4357-4363, 2017.
APA
Park, H., Kim, S., & Moon, D. (2017). Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4. Oncology Letters, 13, 4357-4363. https://doi.org/10.3892/ol.2017.6009
MLA
Park, H., Kim, S., Moon, D."Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4". Oncology Letters 13.6 (2017): 4357-4363.
Chicago
Park, H., Kim, S., Moon, D."Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4". Oncology Letters 13, no. 6 (2017): 4357-4363. https://doi.org/10.3892/ol.2017.6009
Copy and paste a formatted citation
x
Spandidos Publications style
Park HJ, Kim SH and Moon DO: Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4. Oncol Lett 13: 4357-4363, 2017.
APA
Park, H., Kim, S., & Moon, D. (2017). Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4. Oncology Letters, 13, 4357-4363. https://doi.org/10.3892/ol.2017.6009
MLA
Park, H., Kim, S., Moon, D."Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4". Oncology Letters 13.6 (2017): 4357-4363.
Chicago
Park, H., Kim, S., Moon, D."Growth inhibition of human breast carcinoma cells by overexpression of regulator of G-protein signaling 4". Oncology Letters 13, no. 6 (2017): 4357-4363. https://doi.org/10.3892/ol.2017.6009
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