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    Adhesion of beta1 integrin to fibronectin regulates CAM-DR phenotype via p21(WAF1/cip1) in HL60 acute myeloid leukemia (AML) cells
    (Tubitak Scientific & Technical Research Council Turkey, 2008) Canpinar, Hande; Esendagli, Gunes; Kansu, Emin; Ozcan, Aysen Gunel; Guc, Dicle
    Aims: Drug resistance is a major obstacle for a successful cancer therapy. Cell adhesion mediated drug resistance (CAM-DR) is a novel type of drug resistance and generated via interaction of cancer cells with the microenvironment. In this study, CAM-DR phenotype was analyzed in HL60 acute myeloid leukemia (AML) cells. Materials and Methods: Fibronectin (FN) adherence of HL60 cells was tested by a colorimetric adhesion assay. Flow cytometry analyses were performed to evaluate doxorubicin-incluced apoptosis and to determine cell cycle status. Proliferation rate was evaluated by [H-3]-thymidine incorporation assay. Western blot and RTPCR were used for analysis of the factors involved in cell cycle control. Results: Binding of HL60 to FN via alpha 4 beta 1 and alpha 5 beta 1 integrins exerted a CAM-DR phenotype, which shows resistance to apoptosis triggered by doxorubicin. FN-adherent HL60 cells accumulated in the G(0)/G(1) phase of cell cycle and stopped proliferation. However, after detachment from FN, cells entered S phase, proliferated, and became sensitive to apoptosis. The analysis of the factors involved in the G(0)/G(1) cell cycle checkpoint showed that CAM-DR phenotype might be regulated mainly by p21(waf/cip). Conclusions: Here we showed that CAM-DR may also represent a reversible drug resistance mechanism that decreases apoptosis and causes growth arrest in AML blasts.