Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity.
Caveolin-1 expression and function were investigated in human colon cancer. Low levels of caveolin-1 mRNA and protein were detected in several colon carcinoma cell lines. Moreover, caveolin-1 protein levels were significantly reduced in human tumor epithelial mucosa (3.6 +/- 1.4-fold) when compared with normal colon mucosa for a majority (10 of 15) of the patients characterized. To directly assess the role of caveolin-1 in tumor development, caveolin-1 was reexpressed in the HT29 and DLD1 colon carcinoma cells, and the resulting HT29-cav-1 or DLD1-cav-1 cells were tested for tumorigenicity in nude mice. In most experiments, tumor formation was either blocked or retarded for HT29-cav-1 cells (10 of 13 mice) and DLD1-cav-1 cells (5 of 7 mice), as compared with both mock-transfected and parental HT29 or DLD1 cells. Interestingly, basal caveolin-1 levels were significantly reduced in HT29-cav-1 and DLD1-cav-1 cells isolated from tumors. Likewise, endogenous caveolin-1 mRNA and protein levels were found to be reduced in NIH-3T3 cells recovered from tumors after injection into nude mice. Thus, reexpression of caveolin-1 in colon carcinoma lines reduced the probability of tumor formation in vivo, and when tumors did develop from either HT29-cav-1, DLD1-cav-1, or NIH-3T3 cells, lower basal levels of caveolin-1 were detected. Finally, evidence was obtained indicating that initial caveolin-1 down-regulation in colon cancer cells need not be an entirely irreversible process because cell survival on selection for either drug resistance or increased metastatic potential correlated with increased caveolin-1 expression levels.
Bender
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Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Reymond
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MA
Bron
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Quest
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AF
D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis* / Q000235:genetics; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D008727:Methotrexate