Metabolic Transformation of Normal Human Melanocytes Under Extracellular Stimuli
2012
Demidem, Aïcha | Morvan, Daniel | Steyaert, Jean Marc | Israël, Maurice | Schwartz, Laurent | Unité de Nutrition Humaine (UNH) ; Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université | École polytechnique (X) ; Institut Polytechnique de Paris (IP Paris) | Soc Biorebus ; Partenaires INRAE | Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) | Institut National de la Sante et de la Recherche Medicale (INSERM); Biorebus Society
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Показать больше [+] Меньше [-]Английский. Previous studies have suggested a link between cancer types and pathophysiological conditions associated to hyperinsulinemia such as type 2 diabetes, metabolic syndrome, obesity and chronic inflammation. In this report we investigated the link between hyperinsulinemia and cancer. As end points of transformation, the following criteria were used, including cell proliferation rate, soft agar colony formation, DNA content and methylation status, karyotype, oncoprotein transcription, expression and activity (PP2A, Akt/PAkt, cMyc, PTEN, PP1 and Ras). Previously, we and others found that PP2A activity controlled Akt and cMyc expression was decreased during carcinogenesis. Normal melanocyte cultures were exposed to high insulin and glucose concentrations added for 3 weeks. After 4 to 5 weeks, melanocytes exhibited shortened doubling time (2.7 days vs 5.6 days, Treated vs Control, P < 0.01). After three weeks treatment followed by 1 or 2 week(s) of culture in standard medium, treated melanocytes only were able to grow in soft agar colonies. Methylation of the catalytic subunit of PP2A was decreased (-40%, P < 0.001) and PP2A phosphatase activity reduced. Oncoprotein expression was altered with increased expression of PAkt (+35%, P < 0.01), Akt (+25%, P < 0.01) and c-Myc (+ 40%, P < 0.001), a weak increase of PP1 expression (+ 10%). In conclusion chronic exposure to insulin and glucose appear promotes normal human melanocyte transformation. It is probable that increased metabolism such as seen in inflammation plays a key role in carcinogenesis
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