Rosiglitazone, an Agonist of PPAR<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="E1"><mml:mi>γ</mml:mi></mml:math>, Inhibits Non-Small Cell Carcinoma Cell Proliferation In Part through Activation of Tumor Sclerosis Complex-2

Han, ShouWei; Zheng, Ying; Roman, Jesse

doi:10.1155/2007/29632

Cited by 19 publications

(17 citation statements)

References 32 publications

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“…Experiments using whole lung homogenates do not permit the identification of changes in gene expression or protein synthesis in selected cell populations, such as airway epithelia, endothelial cells, or interstitial cells. RGZ, one of the thiazolidinedione derivatives, is generally considered one of the most potent and selective synthetic ligands of PPAR-␥ but may also exhibit some non-PPAR-␥-mediated effects (15,19). Our studies demonstrate a reduction in TGF-␤ signaling with a PPAR-␥ agonist and an increase in PPAR-␥ and its signaling with inhibition of TGF-␤ but do not identify a mechanism by which these processes occur.…”

Section: Discussioncontrasting

confidence: 54%

Hypoxia-induced inhibition of lung development is attenuated by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Nicola¹,

Ambalavanan

Zhang³

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hypoxia enhances transforming growth factor-β (TGF-β) signaling, inhibiting alveolar development and causing abnormal pulmonary arterial remodeling in the newborn lung. We hypothesized that, during chronic hypoxia, reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling may contribute to, or be caused by, excessive TGF-β signaling. To determine whether PPAR-γ was reduced during hypoxia, C57BL/6 mice were exposed to hypoxia from birth to 2 wk and evaluated for PPAR-γ mRNA and protein. To determine whether rosiglitazone (RGZ, a PPAR-γ agonist) supplementation attenuated the effects of hypoxia, mice were exposed to air or hypoxia from birth to 2 wk in combination with either RGZ or vehicle, and measurements of lung histology, function, parameters related to TGF-β signaling, and collagen content were made. To determine whether excessive TGF-β signaling reduced PPAR-γ, mice were exposed to air or hypoxia from birth to 2 wk in combination with either TGF-β-neutralizing antibody or vehicle, and PPAR-γ signaling was evaluated. We observed that hypoxia reduced PPAR-γ mRNA and protein, in association with impaired alveolarization, increased TGF-β signaling, reduced lung compliance, and increased collagen. RGZ increased PPAR-γ signaling, with improved lung development and compliance in association with reduced collagen and TGF-β signaling. However, no reduction was noted in hypoxia-induced pulmonary vascular remodeling. Inhibition of hypoxia-enhanced TGF-β signaling increased PPAR-γ signaling. These results suggest that hypoxia-induced inhibition of lung development is associated with a mutually antagonistic relationship between reduced PPAR-γ and increased TGF-β signaling. PPAR-γ agonists may be of potential therapeutic significance in attenuating TGF-β signaling and improving alveolar development.

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Section: Discussioncontrasting

confidence: 54%

Hypoxia-induced inhibition of lung development is attenuated by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Nicola¹,

Ambalavanan

Zhang³

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Further work revealed that rosiglitazone increased the phosphorylation of AMP-activated protein kinase α, a target of LKB1, and tuberous sclerosis complex 2 (TSC2), another potential tumor suppressor and upstream downregulator of mTOR. The latter pathway was independent of PPARγ since GW9662 and PPARγ siRNA did not affect it [54,55] ; others have shown similar increases in PTEN expression induced by rosiglitazone [56] . One recent study showed that troglitazone may bind directly to EGFR, inhibit its signaling, and stimulate its internalization independent of PPARγ in several cells including lung cancer cells [41] .…”

Section: Pparγ Ligands and Kinase Signaling Pathwaysmentioning

confidence: 95%

Anticancer actions of PPARγ ligands: Current state and future perspectives in human lung cancer

Han

Roman²

2010

WJBC

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Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily. Of the three PPARs identified to date (PPARγ, PPARβ/δ, and PPARα), PPARγ has been studied the most, in part because of the availability of PPARγ agonists (also known as PPARγ ligands) and its significant effects on the management of several human diseases including type 2 diabetes, metabolic syndrome, cardiovascular disease and cancers. PPARγ is expressed in many tumors including lung cancer, and its function has been linked to the process of lung cancer development, progression and metastasis. Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands. Furthermore, data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer. This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.

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“…PPARÁ is expressed in a variety of normal tissues where it plays an important role in metabolic diseases, and cancer (6)(7)(8). PPARÁ is also highly expressed in many tumors and cancer cell lines derived, for instance, from colon (9), breast (10), lung (11), thyroid (12) and gastric (13) tumors. PPARÁ agonists have been extensively investigated as potential anti-tumor drugs, and they have been shown to inhibit growth of malignant human cells, and cause cell cycle arrest and apoptosis in a broad spectrum of epithelial derived tumor cell lines in vitro (14,15).…”

Section: Introductionmentioning

confidence: 99%

PPARγ is functionally expressed in clear cell renal cell carcinoma

Collet

Théoleyre²,

Rageul³

et al. 2011

Int J Oncol

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Abstract. Peroxisome proliferator-activated receptor gamma (PPARÁ) agonists have been demonstrated to exert an inhibitory effect on cell growth in several tumor models, including clear cell renal cell carcinoma (CCRCC). PPARÁ has therefore been proposed to be a potential therapeutic target. Thus, the PPARÁ gene must be expressed and not altered in cancer cells. We have therefore analyzed tumor specimens collected from 63 patients with CCRCC who underwent partial or total nephrectomy. The multiplex ligation-dependent probe amplification (MLPA) assay was used to detect deletions in the PPARÁ gene. The majority of the tumors (48/63; 76.2%) did not present alterations. Two samples (3.2%) presented a deletion of the non-coding exon A1. Nine samples (14.3%) showed large heterozygous deletions in chromosome 3p including PPARÁ. Potential mutations were analyzed by DNA sequencing of the 6 coding exons of the PPARÁ gene. No mutation was found in exons 1-5. In exon 6, a silent polymorphism was detected in 14 samples (22.2%). CCRCC were found to express the PPARÁ1 isoform. The expression level of PPARÁ was measured by real-time quantitative PCR. A significantly reduced transcript level was associated with an elevated Fuhrman grade. Finally, we analyzed the expression of angiopoietin-like 4, a known PPARÁ target gene, in CCRCC cell lines cultured in the presence of rosiglitazone, a PPARÁ agonist. A strong induction was found in the 3 cell lines tested, indicating that PPARÁ is functional in all these cell lines. In conclusion, we show here that PPARÁ is expressed and functional in CCRCC, prerequisites for being a potential target for CCRCC treatment.

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Rosiglitazone, an Agonist of PPARγ, Inhibits Non-Small Cell Carcinoma Cell Proliferation In Part through Activation of Tumor Sclerosis Complex-2

Cited by 19 publications

References 32 publications

Hypoxia-induced inhibition of lung development is attenuated by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Hypoxia-induced inhibition of lung development is attenuated by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

Anticancer actions of PPARγ ligands: Current state and future perspectives in human lung cancer

PPARγ is functionally expressed in clear cell renal cell carcinoma

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