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      Expression of the Wilms’ tumour gene and its association with PPARβ/δ in healthy skin and melanoma of horses

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          Abstract

          The Wilms’ tumour gene ( WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARβ/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARβ/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in healthy skin, mainly in the epidermis, hair follicle, sebaceous gland and sweat gland, while no expression was observed in equine melanoma tissues. Moreover, it was observed that PPARβ/δ has a basal expression in healthy skin and that it is overexpressed in melanoma. These results were confirmed by a densitometric analysis, where a significant increase of the WT1-positive area was observed in healthy skin (128.66 ± 19.84 pixels 10 6) compared with that observed in melanoma (1.94 ± 0.04 pixels 10 6). On the other hand, a positive area with an expression of PPARβ/δ in healthy skin (214.94 ± 11.85 pixels 10 6) was significantly decreased compared to melanoma (624.86 ± 181.93 pixels 10 6). These data suggest that there could be a regulation between WT1 and PPARβ/δ in this disease in horses.

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          Most cited references23

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          The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases

          Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of the following three subtypes: PPARα, PPARγ, and PPARβ/δ. Activation of PPAR-α reduces triglyceride level and is involved in regulation of energy homeostasis. Activation of PPAR-γ causes insulin sensitization and enhances glucose metabolism, whereas activation of PPAR-β/δ enhances fatty acids metabolism. Thus, PPAR family of nuclear receptors plays a major regulatory role in energy homeostasis and metabolic function. The present review critically analyzes the protective and detrimental effect of PPAR agonists in dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity.
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            PPARdelta regulates glucose metabolism and insulin sensitivity.

            The metabolic syndrome is a collection of obesity-related disorders. The peroxisome proliferator-activated receptors (PPARs) regulate transcription in response to fatty acids and, as such, are potential therapeutic targets for these diseases. We show that PPARdelta (NR1C2) knockout mice are metabolically less active and glucose-intolerant, whereas receptor activation in db/db mice improves insulin sensitivity. Euglycemic-hyperinsulinemic-clamp experiments further demonstrate that a PPARdelta-specific agonist suppresses hepatic glucose output, increases glucose disposal, and inhibits free fatty acid release from adipocytes. Unexpectedly, gene array and functional analyses suggest that PPARdelta ameliorates hyperglycemia by increasing glucose flux through the pentose phosphate pathway and enhancing fatty acid synthesis. Coupling increased hepatic carbohydrate catabolism with its ability to promote beta-oxidation in muscle allows PPARdelta to regulate metabolic homeostasis and enhance insulin action by complementary effects in distinct tissues. The combined hepatic and peripheral actions of PPARdelta suggest new therapeutic approaches to treat type II diabetes.
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              Immunohistochemical detection of WT1 protein in a variety of cancer cells.

              WT1 was first identified as a tumor suppressor involved in the development of Wilms' tumor. Recently, oncogenic properties of WT1 have been demonstrated in various hematological malignancies and solid tumors. Because WT1 has been identified as a molecular target for cancer immunotherapy, immunohistochemical detection of WT1 in tumor cells has become an essential part of routine practice. In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. Staining for C-19 and 6F-H2 was found in 35-100 and 5-88% of the cases of each kind of tumor, respectively. WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. Immunohistochemical detection with routinely processed histologic sections could provide meaningful information on the expression of WT1 in cancer cells.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Acta Veterinaria Hungarica
                Akademiai Kiado Zrt.
                0236-6290
                1588-2705
                April 19 2021
                April 19 2021
                : 68
                : 4
                : 374-379
                Affiliations
                [1 ]1Department of Genetics, Faculty of Medicine Veterinary and Zootechnics, Autonomous University of Nuevo León, Av. Francisco Villa s/n, Ex Hacienda el Canadá, 66050 Gral. Escobedo, NL, Mexico
                [2 ]2Department of Histology, Faculty of Medicine, Autonomous University of Nuevo León, Mexico
                [3 ]3Northeast Biomedical Research Centre (CIBIN) of the IMSS, Monterrey, NL, Mexico
                [4 ]4Laboratory of Immunology and Virology, Faculty of Biological Sciences, Autonomous University of Nuevo León, Mexico
                [5 ]5Department of Parasitology, Faculty of Medicine Veterinary and Zootechnics, Autonomous University of Nuevo León, Mexico
                [6 ]6Department of Virology, Faculty of Medicine Veterinary and Zootechnics, Autonomous University of Nuevo León, Mexico
                Article
                10.1556/004.2020.00045
                80c8864b-ab01-4ea6-b697-2f6416483d84
                © 2021
                History

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