Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells

Wenwen Chien, Dong Yin, Dorina Gui, Akio Mori, Jonathan Mordechai Frank, Jonathan Said, Donato Kusuanco, Alberto Marchevsky, Robert McKenna, H. Phillip Koeffler

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF) is a secreted protein that belongs to CCN family. The proteins In this family are implicated in various biological processes, such as angiogenesis, adhesion, migration, and apoptosis. In this study, we explored the roles of CTGF in lung tumorigenesis. The expression levels of CTGF in 58 lung cancer samples were reduced by >2 fold in 57% of the samples compared with matched normal samples using real-time reverse transcription-PCR. These results were confirmed by immunohistochemical staining for CTGF in normal lung epithelia and lung cancer. Cellular proliferation was inhibited in non-small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression. Partially purified CTGF suppressed lung cancer cell growth. The growth Inhibition caused by CTGF overexpression was associated with growth arrest at G0-G1 and prominent induction of p53 and ADP ribosylation factor. Most interestingly, overexpression of CTGF suppressed insulin-like growth factor-I-dependent Akt phosphorylation and epidermal growth factor-dependent extracellular signal-regulated kinase 1/2 phosphorylation. In summary, NSCLC cells expressed decreased levels of CTGF compared with normal lung cells; this lower expression has an effect on lung cancer cell proliferation and its cellular response to growth factors. Our data suggest that CTGF may behave as a secreted tumor suppressor protein in the normal lung, and its expression is suppressed in many NSCLCs.

Original languageEnglish (US)
Pages (from-to)591-598
Number of pages8
JournalMolecular Cancer Research
Volume4
Issue number8
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

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Connective Tissue Growth Factor
Non-Small Cell Lung Carcinoma
Cell Proliferation
Lung Neoplasms
Lung
Growth
Phosphorylation
ADP-Ribosylation Factors
Tumor Suppressor Proteins
Biological Phenomena
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Insulin-Like Growth Factor I
Epidermal Growth Factor
Reverse Transcription
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Proteins
Epithelium
Apoptosis

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells. / Chien, Wenwen; Yin, Dong; Gui, Dorina; Mori, Akio; Frank, Jonathan Mordechai; Said, Jonathan; Kusuanco, Donato; Marchevsky, Alberto; McKenna, Robert; Koeffler, H. Phillip.

In: Molecular Cancer Research, Vol. 4, No. 8, 01.08.2006, p. 591-598.

Research output: Contribution to journalArticle

Chien, W, Yin, D, Gui, D, Mori, A, Frank, JM, Said, J, Kusuanco, D, Marchevsky, A, McKenna, R & Koeffler, HP 2006, 'Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells', Molecular Cancer Research, vol. 4, no. 8, pp. 591-598. https://doi.org/10.1158/1541-7786.MCR-06-0029
Chien, Wenwen ; Yin, Dong ; Gui, Dorina ; Mori, Akio ; Frank, Jonathan Mordechai ; Said, Jonathan ; Kusuanco, Donato ; Marchevsky, Alberto ; McKenna, Robert ; Koeffler, H. Phillip. / Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells. In: Molecular Cancer Research. 2006 ; Vol. 4, No. 8. pp. 591-598.
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