The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages |
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Authors: | Engel T Lorkowski S Lueken A Rust S Schlüter B Berger G Cullen P Assmann G |
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Institution: | Peptide Chemistry Research Group, Semmelweis University, Budapest, H-1088 Hungary. stetak@hotmail.com |
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Abstract: | The heptapeptide TT-232 is structurally related to the hypothalamic hormone somatostatin and shows promise as an anticancer drug because of its tumor-specific cytotoxic effects. Apart from the ability to induce apoptosis, the synthetic peptide can trigger an alternative pathway that leads to cell cycle arrest in certain tumor cell systems. We found that pulse treatment with TT-232 blocks the cell cycle G(1)/S transition irreversibly in A431 cells. Investigation of the TT-232 signaling pathway yielded results similar to those reported for somatostatin although its affinity to the somatostatin receptor 1 is significantly reduced. We show that functional protein kinase C (PKC) delta as well as c-Src are necessary mediators of the TT-232 cytostatic effect and we propose a signaling pathway that leads to cell cycle arrest. |
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