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; Putten, Vicki Van; Chan, Daniel C.; Winn, Robert A.; Geraci, Mark W.; Nemenoff, Raphael A.

doi:10.1038/sj.onc.1208333

Cited by 104 publications

(106 citation statements)

References 46 publications

(47 reference statements)

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“…Limited information is available on factors that regulate transcription of endogenous DLC1, however. Activation of peroxisome proliferator-activated receptor γ (PPARγ), which inhibits the growth of breast and prostate cancer cells as well as metastasis of lung tumor cells, was shown to increase expression of DLC1 in association with inhibition of the invasiveness of lung cancer cells that overexpress PPARγ [9]. All-trans retinoic acid inhibits the proliferation of normal cells as well as that of various types of tumor cells, and culture of Wilms' tumor cells with alltrans-retinoic acid induced expression of DLC1 [10].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Ullmannova

Popescu

2007

Cancer Detection and Prevention

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Background-Dietary flavone was previously shown to increase the expression of deleted in liver cancer-1 gene (DLC-1) in HT-29 colon carcinoma cell line (Proteomics 2004;4:2455-64). DLC-1 that encodes a Rho GTPase-activating protein, functions as a tumor suppressor gene and is frequently inactivated or down-regulated in several common cancers. Restoration of DLC-1 expression suppresses in vitro tumor cells proliferation and tumorigenicity in vivo.Methods-Here, the effect of flavone was examined in several DLC-1-deficient cell lines derived from different types human cancer using assays for cell proliferation, gene expression and transfer.Results-We show that exposure to 15μM flavone increased DLC1 expression in breast but not in liver or prostate carcinoma cells or a nonmalignant breast epithelial cell line. Flavone restored the expression of DLC1 in the breast carcinoma cell lines MDA-MB-468, MDA-MB-361, and BT20 as well as in the colon carcinoma cell line HT-29 all of which are DLC-1-negative due to promoter hypermethylation. We further show that flavone inhibited cell proliferation, induced cell cycle arrest at G2-M, increased p21 Waf1 gene expression, and caused apoptosis. Microarray analysis of these aggressive and metastatic breast carcinoma cells revealed 29 flavone-responsive genes, among which the DNA damage-inducible GADD genes were up-regulated and the proto-oncogene STMN1 and IGFBP3 were down-regulated.Conclusions-Flavone-mediated alterations of genes that regulate tumor cell proliferation, cell cycle, and apoptosis contribute to chemopreventive and antitumoral effects of flavone. Alone or in combination with demethylating agents, flavone may be an effective adjunct to chemotherapy in preventing breast cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Ullmannova

Popescu

2007

Cancer Detection and Prevention

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“…In the current study, we have demonstrated that PGE 2 , through its receptor(s) leads to enhanced proliferation through activation of the ␤-catenin pathway, and an impairment in formation of hollow acinar structures by inhibiting apoptosis. These findings are recapitulated in NSCLC expressing K-Ras, where cells form organized acinar structures, but fail to hollow out (Bren-Mattison et al, 2005). Simultaneously, ERK activation is critical for the induction of MMP-9 through a COX-2-independent pathway.…”

Section: Discussionmentioning

confidence: 51%

“…RL-65 cells were chosen because they represent a spontaneously immortalized cell line, have high levels of E-cadherin expression, form a high-resistance epithelium in two-dimensional tissue culture, and form hollowed-out acinar structures in threedimensional Matrigel cultures (Bren-Mattison et al, 2005). To validate functional expression of K-Ras, cells were evaluated for activation of downstream signaling pathways.…”

Section: K-ras Expression Effects On Increased Proliferation and Delamentioning

confidence: 99%

“…For 2D cultures, cells were plated at 5000 cells/ml into eight-well chamber slides and grew 3 d for colony formation. For 3D culture, cells were imbedded in RL-65 cell growth medium with 4% Matrigel and evaluated at day 5 and day 8 as described previously (Bren-Mattison et al, 2005). Protein extracts from 3D cultures were prepared by treating cultures with Dispase to digest the Matrigel.…”

Section: Reagentsmentioning

confidence: 99%

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Oncogenic K-Ras Regulates Proliferation and Cell Junctions in Lung Epithelial Cells through Induction of Cyclooxygenase-2 and Activation of Metalloproteinase-9

Wang¹,

Li²,

Putten³

et al. 2009

MBoC

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“…12,24,44,[102][103][104][105][106] For example, in addition to modulating inflammation, there is growing evidence that NSAIDs (e.g., sulindac sulfide and indomethacin), as well as TZDs, may promote epithelial-cell differentiation by activating PPARg. 12,103 This was observed in vitro and in animal tumor models 107 for both nonsmall-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) lines. The overexpression of PPARg in these models also inhibited tumor growth.…”

Section: Lung Cancermentioning

confidence: 91%

Peroxisome Proliferator‐Activated Receptors: Potential Therapeutic Targets in Lung Disease?

Denning

Stoll

2005

Pediatric Pulmonology

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The peroxisome proliferator‐activated receptors (PPARs) are a family of nuclear hormone receptors that play central roles in lipid and glucose homeostasis, cellular differentiation, and the immune/inflammatory response. Growing evidence indicates that changes in expression and activation of PPARs likely modulate conditions as diverse as diabetes, atherosclerosis, cancer, asthma, Parkinson's disease, and Alzheimer's disease. Activation of these receptors by natural or pharmacologic ligands leads to both gene‐dependent and gene‐independent effects that alter the expression of a wide array of proteins. In the lung, PPARs are expressed by alveolar macrophages, as well as by epithelial, endothelial, and smooth muscle cells. Studies both in vitro and in vivo suggest that PPAR ligands may have anti‐inflammatory effects in asthma, pulmonary sarcoidosis, and pulmonary alveolar proteinosis, as well as antiproliferative and antiangiogenic effects in epithelial lung cancers. Further studies to understand the contribution of these receptors to health and disease will be important for determining whether they represent a promising target for therapeutic intervention. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.

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

Cited by 104 publications

References 46 publications

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines

Oncogenic K-Ras Regulates Proliferation and Cell Junctions in Lung Epithelial Cells through Induction of Cyclooxygenase-2 and Activation of Metalloproteinase-9

Peroxisome Proliferator‐Activated Receptors: Potential Therapeutic Targets in Lung Disease?

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