Peroxisome proliferator-activated receptor-γ (PPARγ) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC)

Yvette Bren-Mattison, Vicki Van Putten, Daniel Chan, Robert Winn, Mark W. Geraci, Raphael A. Nemenoff

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Pharmacological activators of peroxisome proliferator-activated receptor-γ (PPARγ) have been shown to inhibit growth of lung tumors largely through growth inhibition and induction of apopotosis. However, since many of these agents engage other effectors, the role of PPARγ in lung tumorigenesis remains poorly defined. To specifically examine PPARγ-mediated events, non-small-cell lung cancer (NSCLC) cells overexpressing PPARγ were established. Overexpression of PPARγ in H2122 adenocarcinoma cells (H2122-PPARγ) blocked anchorage-independent growth compared to cells transfected with empty vector (H2122-LNCX), but had no significant effect on cell proliferation or apoptosis under standard tissue culture conditions. Orthotopic implantation of H2122-PPARγ cells into the lungs of nude rats inhibited tumor growth and metastasis in vivo and prolonged survival compared to implantation of H2122-LNCX cells. Consistent with these findings, H2122-PPARγ cells had an impaired invasiveness as assessed in Transwell assays. In a three-dimensional culture system, H2122-PPARγ cells formed polarized spheroid structures similar to those observed with normal lung epithelial cells. H2122-LNCX cells formed nonpolarized aggregate structures and did not show any of these epithelial properties. These data indicate that inhibitory effects of PPARγ on lung tumorigenesis involve selective inhibition of invasive metastasis, and activation of pathways that promote a more differentiated epithelial phenotype.

Original languageEnglish (US)
Pages (from-to)1412-1422
Number of pages11
JournalOncogene
Volume24
Issue number8
DOIs
StatePublished - Feb 17 2005
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Non-Small Cell Lung Carcinoma
Carcinogenesis
Phenotype
Lung
Growth
Nude Rats
Neoplasm Metastasis
Neoplasms
Adenocarcinoma
Epithelial Cells
Cell Proliferation
Pharmacology
Apoptosis

Keywords

  • Differentiation
  • Metastasis
  • Non-small-cell lung cancer
  • PPARγ
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Peroxisome proliferator-activated receptor-γ (PPARγ) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC). / Bren-Mattison, Yvette; Van Putten, Vicki; Chan, Daniel; Winn, Robert; Geraci, Mark W.; Nemenoff, Raphael A.

In: Oncogene, Vol. 24, No. 8, 17.02.2005, p. 1412-1422.

Research output: Contribution to journalArticle

Bren-Mattison, Yvette ; Van Putten, Vicki ; Chan, Daniel ; Winn, Robert ; Geraci, Mark W. ; Nemenoff, Raphael A. / Peroxisome proliferator-activated receptor-γ (PPARγ) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC). In: Oncogene. 2005 ; Vol. 24, No. 8. pp. 1412-1422.
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