The Role of PPARs in the Endothelium: Implications  for Cancer Therapy

Bishop‐Bailey, David; Swales, Karen E.

doi:10.1155/2008/904251

Cited by 27 publications

(22 citation statements)

References 133 publications

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“…Interestingly, none of these genes were differentially transcribed (DE) (Supplementary Table 3). As expected, based on previous findings, RAR Activation and Protein Kinase A Signaling were also enriched (30,31). The top three pathways in Figure 4.A lack an activation score because they include findings without associated directional attributes necessary for activity prediction by IPA.…”

Section: Resultssupporting

confidence: 88%

Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a global decrease in H3K4me3 activity

Triff

McLean

Konganti

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model. Carcinogen (AOM) effects were detected genome-wide at the RNA (116 DE genes), K9ac (49 DERs including 24 genes) and K4me3 (7678 DERs including 3792 genes) level. RNA-seq differential expression and pathway analysis indicated that interferon-associated innate immune responses were impacted by AOM exposure. Despite extensive associations between K4me3 DERs and colon tumorigenesis (1210 genes were linked to colorectal carcinoma) including FOXO3, GNAI2, H2AFX, MSH2, NR3C1, PDCD4 and VEGFA, these changes were not reflected at the RNA gene expression level during early cancer progression. Collectively, our results indicate that carcinogen-induced changes in gene K4me3 DERs are harbingers of future transcriptional events, which drive malignant transformation of the colon.

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Section: Resultssupporting

confidence: 88%

Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a global decrease in H3K4me3 activity

Triff

McLean

Konganti

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…In the lipomas examined, very few PPARδ‐positive fat cells could be observed, two of five lipomas showed no PPARδ immunoreactivity in the lipocytes, and three exhibited focal PPARδ expression in the adipose tissue component, with 10–25% positive lipocytes. Endothelial cells and lymphocytes in the surrounding tissue displayed a strong nuclear PPARδ expression and served as an internal positive control (Figure 1A) 17, 18.…”

Section: Resultsmentioning

confidence: 99%

Peroxisome proliferator‐activated receptor β/δ (PPARβ/δ) is highly expressed in liposarcoma and promotes migration and proliferation

Wagner

Benchetrit

Bianchini

et al. 2011

The Journal of Pathology

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Aberrations of specialized metabolic pathways might be implicated in the development of neoplasias. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with important functions in metabolism. PPARβ/δ and PPARγ act in the proliferation and differentiation of adipose tissue progenitor cells. Thus, a potential use of PPARγ agonists for the treatment of liposarcoma had been suggested, but clinical trials failed to detect beneficial effects. We show here that PPARδ is highly expressed in liposarcoma compared to lipoma and correlates with proliferation. Stimulation of liposarcoma cell lines with a specific PPARδ agonist increases proliferation, which is abolished by a PPARδ-siRNA or a specific PPARδ antagonist. Expression of the adipose tissue secretory factor leptin is lower in liposarcoma compared to lipoma and leptin reduces proliferation of liposarcoma cell lines. PPARδ activation stimulates cell migration whereas leptin diminishes it. We demonstrate that PPARδ directly represses leptin as: (a) leptin becomes down-regulated upon PPARδ activation; (b) PPARδ represses leptin promoter activity in different sarcoma cell lines; (c) deletion of a PPAR/RxR binding element in the leptin promoter abolishes repression by PPARδ; and (d) in chromatin immunoprecipitation we confirm in vivo binding of PPARδ to the leptin promoter. Our data suggest inhibition of PPARδ as a potential novel strategy to reduce liposarcoma cell proliferation.

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“…PPARγ is expressed in various cancer types including prostate, colon, breast cancers, etc., where it has been reported to be a pro-apoptotic and anti-proliferative agent. PPARγ ligands have also been found to be major drug development targets for cancer prevention [32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

The role of NF-κB and PPARγ in experimentally induced colorectal cancer and chemoprevention by cyclooxygenase-2 inhibitors

2010

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Initiation of malignancy is dependent upon the basic ratio of cell proliferation and apoptosis. Many molecular proteins and pathways are responsible for the imbalance of proliferation and apoptosis ratio. For example, Akt is a key biomolecule which regulates the cell survival signals via various downstream pathways. One of those pathways is nuclear factor-κB activation which also regulates many downstream pathways that are essential for cell survival. Along with these anti-apoptotic pathways, cells do have a parallel mechanism to prevent malignancy with the help of the ligand-induced nuclear receptors, e.g., peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been found to be expressed in many cancer cell types and reported to be a pro-apoptotic transcription factor. The study aimed to observe the ability of two cyclooxygenase-dependent non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of experimentally induced early neoplasm of colon via NF-κB and PPARγ pathways. Early stages of colorectal cancer were produced in rats with 1,2-dimethylhydrazine dihydrochloride. Western blotting and immunohistochemistry were performed along with morphological and histological analysis. According to the expression levels of NF-κB and PPARγ in the cell nuclei, it is observed that NSAIDs may prevent colorectal cancer in the early stages by a concomitant down-regulation of NF-κB and up-regulation of PPARγ. COX-independent mechanism of anti-carcinogenesis was observed by COX-dependent NSAIDs in colorectal cancer.

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The Role of PPARs in the Endothelium: Implications for Cancer Therapy

Cited by 27 publications

References 133 publications

Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a global decrease in H3K4me3 activity

Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a global decrease in H3K4me3 activity

Peroxisome proliferator‐activated receptor β/δ (PPARβ/δ) is highly expressed in liposarcoma and promotes migration and proliferation

The role of NF-κB and PPARγ in experimentally induced colorectal cancer and chemoprevention by cyclooxygenase-2 inhibitors

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