Abstract
CD43 is a highly glycosylated transmembrane protein expressed on the surface of most hematopoietic cells. Expression of CD43 has also been demonstrated in many human tumor tissues, including colon adenomas and carcinomas, but not in normal colon epithelium. The potential contribution of CD43 to tumor development is still not understood. Here, we show that overexpression of CD43 increases cell growth and colony formation in mouse and human cells lacking expression of either p53 or ARF (alternative reading frame) tumor-suppressor proteins. In addition, CD43 overexpression also lowers the detection of the FAS death receptor on the cell surface of human cancer cells, and thereby helps to evade FAS-mediated apoptosis. However, when both p53 and ARF proteins are present, CD43 overexpression activates p53 and suppresses colony formation due to induction of apoptosis. These observations suggest CD43 as a potential contributor to tumor development and the functional ARF–p53 pathway is required for the elimination of cells with aberrant CD43 expression.
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Acknowledgements
We are grateful to Dr K Wiman for the p14ARF cDNA and for ARF-null MEFs and Dr Ch Sherr for p19ARF cDNA. This project has been supported by grants from Estonian Science Foundation (ETF6459), by Grant QLRT-2001-2821 from the European Commission, the Swedish Cancer Foundation, the Swedish Institute, and Ingabritt and Arne Lundberg Foundation.
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Kadaja-Saarepuu, L., Laos, S., Jääger, K. et al. CD43 promotes cell growth and helps to evade FAS-mediated apoptosis in non-hematopoietic cancer cells lacking the tumor suppressors p53 or ARF. Oncogene 27, 1705–1715 (2008). https://doi.org/10.1038/sj.onc.1210802
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DOI: https://doi.org/10.1038/sj.onc.1210802
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