Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade

Theocharis, Stamatios; Kanelli, Helen; Politi, Ekaterini; Margeli, Alexandra; Karkandaris, Christos; Philippides, Theodoros; Koutselinis, A.

doi:10.1016/s0169-5002(02)00013-2

Cited by 72 publications

(66 citation statements)

References 45 publications

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“…The finding of increased levels of PPARg staining within HCC tissue is consistent with observations in many epithelial-related tumors (3,4,(23)(24)(25) but has not been previously reported for HCC. In one study of five HCC specimens, there was no difference in PPARg protein levels in HCC samples and paired adjacent normal appearing tissue as measured by Western blot analysis (26).…”

Section: Discussionsupporting

confidence: 91%

Peroxisome Proliferator-Activated Receptor γ Inhibition Prevents Adhesion to the Extracellular Matrix and Induces Anoikis in Hepatocellular Carcinoma Cells

et al. 2005

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Activation of the nuclear transcription factor peroxisome proliferator-activated receptor ; (PPAR;) inhibits growth and survival of hepatocellular carcinoma (HCC) cell lines. To further investigate the function of PPAR; in HCC, PPAR; expression patterns in primary tumors were examined, and the responses of two HCC cell lines to PPAR; activation and inhibition were compared. PPAR; expression was increased in HCC and benign-appearing peritumoral hepatocytes compared with remote benign hepatocytes. Both compound PPAR; inhibitors and PPAR; small interfering RNAs prevented HCC cell lines from adhering to the extracellular matrix. Loss of adhesion was followed by caspase-dependent apoptosis (anoikis). PPAR; inhibitors had no effect on initial B B1 integrin-mediated adhesion, or on total focal adhesion kinase levels but did reduce focal adhesion kinase phosphorylation. The PPAR; inhibitor T0070907 was significantly more efficient at causing cancer cell death than the activators troglitazone and rosiglitazone. T0070907 caused cell death by reducing adhesion and inducing anoikis, whereas the activators had no direct effect on adhesion and caused cell death at much higher concentrations. In conclusion, PPAR; overexpression is present in HCC. Inhibition of PPAR; function causes HCC cell death by preventing adhesion and inducing anoikis-mediated apoptosis. PPAR; inhibitors represent a potential novel treatment approach to HCC.

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Section: Discussionsupporting

confidence: 91%

Peroxisome Proliferator-Activated Receptor γ Inhibition Prevents Adhesion to the Extracellular Matrix and Induces Anoikis in Hepatocellular Carcinoma Cells

et al. 2005

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“…In full-term normal placenta, PPARg is strongly expressed in the nuclei of the syncytiotrophoblast, extravillous cytotrophoblast of cell islands and cell columns, whereas in choriocarcinoma, only a few trophoblastic cells show weak staining for PPARg (Capparuccia et al, 2002). Well-differentiated lung adenocarcinomas present increased frequency for PPARg expression compared with moderately and poorly differentiated ones (Theocharis et al, 2002). The expression of PPARg protein is decreased in oesophageal cancer tissues compared with normal oesophageal squamous epithelium (Terashita et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma

et al. 2004

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The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARg in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARg in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARg was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARg expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARg expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARg was observed in high-grade ovarian tumours with PPARg being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARg immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (w 2 ¼ 48.80, Po0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARg in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (Po0.01). These findings suggest an involvement of PPARg in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

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“…The efficacy of these compounds as anticancer agents has been examined in a variety of cancers, including colon, breast, and prostate (5). PPARg expression has also been shown in non -small cell lung carcinoma (NSCLC) cells and was correlated with tumor histologic type and grade (6). Activation of PPARg by troglitazone, ciglitazone, and pioglitazone caused growth inhibition and apoptosis of NSCLC cells (7,8).…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways

Han

Roman

2006

Molecular Cancer Therapeutics

153

131

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Peroxisome proliferator-activated receptors ; (PPAR;) exert diverse effects on cancer cells. Recent studies showed that rosiglitazone, a synthetic ligand for PPAR;, inhibits cell growth. However, the exact mechanisms underlying this effect are still being explored, and the relevance of these findings to lung cancer remains unclear. Here, we report that rosiglitazone reduced the phosphorylation of Akt and increased phosphatase and tensin homologue (PTEN) protein expression in nonsmall cell lung carcinoma (NSCLC) cells (H1792 and H1838), and this was associated with inhibition of NSCLC cell proliferation. These effects were blocked or diminished by GW9662, a specific PPAR; antagonist. However, transfection with a CMX-PPAR;2 overexpression vector restored the effects of rosiglitazone on Akt, PTEN, and cell growth in the presence of GW9662. In addition, rosiglitazone increased the phosphorylation of AMP-activated protein kinase A (AMPKA), a downstream kinase target for LKB1, whereas it decreased phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream target of mammalian target of rapamycin (mTOR). Of note, GW9662 did not affect the phosphorylation of AMPKA and p70S6K protein. The inhibitory effect of rosiglitazone on NSCLC cell growth was enhanced by the mTOR inhibitor rapamycin; however, it was blocked, in part, by the AMPKA small interfering RNA. Taken together, these findings show that rosiglitazone, via up-regulation of the PTEN/AMPK and down-regulation of the Akt/mTOR/p70S6K signal cascades, inhibits NSCLC cell proliferation through PPAR;-dependent and PPAR;-independent signals. [Mol Cancer Ther 2006;5(2):430 -7]

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Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: correlation with histological type and grade

Cited by 72 publications

References 45 publications

Peroxisome Proliferator-Activated Receptor γ Inhibition Prevents Adhesion to the Extracellular Matrix and Induces Anoikis in Hepatocellular Carcinoma Cells

Peroxisome Proliferator-Activated Receptor γ Inhibition Prevents Adhesion to the Extracellular Matrix and Induces Anoikis in Hepatocellular Carcinoma Cells

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma

Rosiglitazone suppresses human lung carcinoma cell growth through PPARγ-dependent and PPARγ-independent signal pathways

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