التفاصيل البيبلوغرافية
| العنوان: |
Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma. |
| المؤلفون: |
Bengochea, A.1,2, De Souza, M. M.1,2, Lefrançois, L.1,2, Le Roux, E.3, Galy, O.1,2, Chemin, I.1,2, Kim, M.4, Wands, J. R.4, Trepo, C.1,2,5, Hainaut, P.3, Scoazec, J.-Y.5,6, Vitvitski, L.1,2, Merle, P.1,2,5 phmerle@lyon.inserm.fr, Lefrançois, L (AUTHOR) |
| المصدر: |
British Journal of Cancer. 7/8/2008, Vol. 99 Issue 1, p143-150. 8p. 1 Color Photograph, 1 Black and White Photograph, 1 Diagram, 2 Charts, 1 Graph. |
| مصطلحات موضوعية: |
*LIVER cancer, *LIVER cells, *HEPATITIS B virus, *CARCINOGENESIS, *FIBROSIS, *VIRAL replication, *CELL lines, *CELL receptors, *COMPARATIVE studies, *GENES, *HEPATOCELLULAR carcinoma, *LIVER tumors, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *EVALUATION research |
| مستخلص: |
Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the beta-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT-PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (beta-catenin, protein kinase C, and C-Jun NH(2)-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis. [ABSTRACT FROM AUTHOR] |
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