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Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas

Item Type:Article
Title:Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas
Creators Name:Wiechen, K. and Sers, C. and Agoulnik, A. and Arlt, K. and Dietel, M. and Schlag, P.M. and Schneider, U.
Abstract:Caveolae are plasma membrane microdomains that have been implicated in the regulation of several intracellular signaling pathways. Previous studies suggest that caveolin-1, the main structural protein of caveolae, could function as a tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated mesenchymal cells including adipocytes, endothelial cells, and smooth muscle cells. To study whether caveolin-1 is a possible tumor suppressor in human mesenchymal tumors, we have analyzed the expression using immunohistochemistry in normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors. Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues. The expression of caveolin-1 was slightly reduced in four of six well-differentiated liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of 20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight synovial sarcomas. The immunohistochemical findings were confirmed by Western blot analysis in a number of tumors. High levels of both the 24-kd {alpha}- and the 21-kd {beta}-isoform of caveolin-1 were detected in the nontumorigenic human fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells, caveolin-1 is strongly down-regulated. We show that the {alpha}-isoform of caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen-activated protein kinase-signaling pathway with the specific inhibitor PD 98059, whereas the specific inhibitor of DNA methylation 5-aza-2′-deoxycytidine only marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we conclude that caveolin-1 is likely to act as a tumor suppressor gene in human sarcomas.
Keywords:Adipose Tissue Neoplasms, Caveolin 1, Caveolins, Cell Division, Cell Line, Cultured Tumor Cells, Down-Regulation, Enzyme Inhibitors, Fibrous Tissue Neoplasms, Flavonoids, Immunohistochemistry, Muscle Tissue Neoplasms, Sarcoma, Transfection, Tumor Suppressor Genes, Vascular Tissue Neoplasms, Western Blotting
Source:American Journal of Pathology
Publisher:American Society for Investigative Pathology
Page Range:833-839
Date:March 2001
Official Publication:http://ajp.amjpathol.org/cgi/content/abstract/158/3/833
PubMed:View item in PubMed

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