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
January-2016 Volume 11 Issue 1

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
January-2016 Volume 11 Issue 1

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

Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma

  • Authors:
    • Zhenyu You
    • Yong Zhou
    • Yuling Guo
    • Wenyan Chen
    • Shaoqing Chen
    • Xiaolang Wang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pharmacy, Peking University, Beijing 100083, P.R. China
  • Pages: 760-766
    |
    Published online on: November 16, 2015
       https://doi.org/10.3892/ol.2015.3922
  • 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

Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential carcinogenic biomarker in certain types of cancer, such as melanoma. However, its function and clinical significance in non‑small cell lung cancer (NSCLC) has not been well studied. Therefore, the present study aimed to analyze the association between ATF2/phosphorylated (p)‑ATF2 expression and NSCLC malignant behavior, and discuss its clinical significance. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the expression of ATF2 in NSCLC cell lines and fresh NSCLC tissue samples. In addition, immunohistochemistry (IHC) was performed to identify the location and expression of ATF2 and p‑ATF2 (threonine 71) in paraffin‑embedded sections of NSCLC and adjacent normal tissue. The results demonstrated that ATF2 was markedly overexpressed in the NSCLC cells and significantly overexpressed in the fresh NSCLC tissues compared with the control cells and samples (86 paraffin-embedded tissue sections), respectively (P<0.01). Further data demonstrated that ATF2 expression levels were significantly increased in tumor tissues compared to normal tissues and ATF2 was located in the cytoplasm and nucleus. ATF2 expression was closely associated with adverse clinical characteristics such as TNM stage (P=0.002), tumor size (P=0.018) and metastasis (P=0.027). In addition, nuclear p‑ATF2 staining was positive in 65/86 samples of NSCLC. Furthermore, the Kaplan‑Meier analysis indicated that patients with high levels of ATF2 and p‑ATF2 expression had a significantly shorter overall survival compared with patients exhibiting a low expression (P<0.01 and P<0.05, respectively). Subsequent in vitro experiments revealed that cell growth decreased following knockdown of ATF2 expression using RNA interference, indicating that ATF2 may suppress cell proliferation. Taken together, the results of the present study demonstrated that ATF2 and p‑ATF2 were significantly overexpressed in NSCLC tissues, and ATF2 and p‑ATF2 overexpression predicted significantly worse outcomes for patients with NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

D'Addario G and Felip E: ESMO guidelines working group: Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 4(Suppl 20): S68–S70. 2009.

3 

McElnay P and Lim E: Adjuvant or neoadjuvant chemotherapy for NSCLC. J Thorac Dis. 6(Suppl 2): S224–S227. 2014.PubMed/NCBI

4 

Ellis PM, Coakley N, Feld R, Kuruvilla S and Ung YC: Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: A systematic review. Curr Oncol. 22:e183–e215. 2015. View Article : Google Scholar : PubMed/NCBI

5 

NSCLC Meta-analyses collaborative group. Arriagada R, Auperin A, et al: Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: Two meta-analyses of individual patient data. Lancet. 375:1267–1277. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Spiro SG, Tanner NT, Silvestri GA, et al: Lung cancer: Progress in diagnosis, staging and therapy. Respirology. 15:44–50. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Lee IT, Lin CC, Cheng SE, Hsiao LD, Hsiao YC and Yang CM: TNF-α induces cytosolic phospholipase A2 expression in human lung epithelial cells via JNK1/2- and p38 MAPK-dependent AP-1 activation. PloS One. 8:e727832013. View Article : Google Scholar : PubMed/NCBI

8 

Bengoa-Vergniory N, Gorroño-Etxebarria I, González Salazar I and Kypta RM: A switch from canonical to noncanonical Wnt signaling mediates early differentiation of human neural stem cells. Stem Cells. 32:3196–3208. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Lopez-Bergami P, Lau E and Ronai Z: Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat Rev Cancer. 10:65–76. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Bhoumik A, Lopez-Bergami P and Ronai Z: ATF2 on the double-activating transcription factor and DNA damage response protein. Pigment Cell Res. 20:498–506. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Lau E and Ronai ZA: ATF2-at the crossroad of nuclear and cytosolic functions. J Cell Sci. 125:2815–2824. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Shah M, Bhoumik A, Goel V, et al: A role for ATF2 in regulating MITF and melanoma development. PLoS Genet. 6:e10012582010. View Article : Google Scholar : PubMed/NCBI

13 

Lau E, Kluger H, Varsano T, et al: PKCε promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 148:543–555. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Varsano T, Lau E, Feng Y, et al: Inhibition of melanoma growth by small molecules that promote the mitochondrial localization of ATF2. Clin Cancer Res. 19:2710–2722. 2013. View Article : Google Scholar : PubMed/NCBI

15 

An JJ, Shi KJ, Wei W, et al: The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo. Cell Death Dis. 4:e9732013. View Article : Google Scholar : PubMed/NCBI

16 

Laskin WB and Miettinen M: Epithelioid sarcoma: New insights based on an extended immunohistochemical analysis. Arch Pathol Lab Med. 127:1161–1168. 2003.PubMed/NCBI

17 

Song H, Ki SH, Kim SG and Moon A: Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res. 66:10487–10496. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Knippen S, Löning T, Müller V, et al: Expression and prognostic value of activating transcription factor 2 (ATF2) and its phosphorylated form in mammary carcinomas. Anticancer Res. 29:183–189. 2009.PubMed/NCBI

19 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C (T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Yamada H and Sano Y: The biotinylation of the rabbit serotonin antibody and its application to immunohistochemical studies using the two-step ABC method. Histochemistry. 83:285–289. 1985. View Article : Google Scholar : PubMed/NCBI

21 

Zhao Y, Li Y, Han J, et al: Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells. Int J Mol Med. 33:703–710. 2014.PubMed/NCBI

22 

Bhoumik A, Huang TG, Ivanov V, et al: An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis. J Clin Invest. 110:643–650. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Maekawa T, Shinagawa T, Sano Y, et al: Reduced levels of ATF-2 predispose mice to mammary tumors. Mol Cell Biol. 27:1730–1744. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Berger AJ, Kluger HM, Li N, et al: Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 63:8103–8107. 2003.PubMed/NCBI

25 

Duffey D, Dolgilevich S, Razzouk S, Li L, Green R and Gorti GK: Activating transcription factor-2 in survival mechanisms in head and neck carcinoma cells. Head Neck. 33:1586–1599. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Knippen S, Löning T, Müller V, et al: Expression and prognostic value of activating transcription factor 2 (ATF2) and its phosphorylated form in mammary carcinomas. Anticancer Res. 29:183–189. 2009.PubMed/NCBI

27 

Zhao Y, Li Y, Han J, et al: Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells. Int J Mol Med. 33:703–710. 2014.PubMed/NCBI

28 

Bhoumik A, Huang TG, Ivanov V, et al: An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis. J Clin Invest. 110:643–650. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Deng X, Liu H, Huang J, et al: Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: Implications for disease progression. Cancer Res. 68:9663–9670. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
You Z, Zhou Y, Guo Y, Chen W, Chen S and Wang X: Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. Oncol Lett 11: 760-766, 2016.
APA
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., & Wang, X. (2016). Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. Oncology Letters, 11, 760-766. https://doi.org/10.3892/ol.2015.3922
MLA
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., Wang, X."Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma". Oncology Letters 11.1 (2016): 760-766.
Chicago
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., Wang, X."Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma". Oncology Letters 11, no. 1 (2016): 760-766. https://doi.org/10.3892/ol.2015.3922
Copy and paste a formatted citation
x
Spandidos Publications style
You Z, Zhou Y, Guo Y, Chen W, Chen S and Wang X: Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. Oncol Lett 11: 760-766, 2016.
APA
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., & Wang, X. (2016). Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. Oncology Letters, 11, 760-766. https://doi.org/10.3892/ol.2015.3922
MLA
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., Wang, X."Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma". Oncology Letters 11.1 (2016): 760-766.
Chicago
You, Z., Zhou, Y., Guo, Y., Chen, W., Chen, S., Wang, X."Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma". Oncology Letters 11, no. 1 (2016): 760-766. https://doi.org/10.3892/ol.2015.3922
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