Adhesion of Beta1 Integrin to Fibronectin Regulates CAM-DR Phenotype via p21WAF1/cip1 in HL60 Acute Myeloid Leukemia (AML) Cells

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-induced apoptosis and to determine cell cycle status. Proliferation rate was evaluated by [3H]-thymidine incorporation assay. Western blot and RT-PCR were used for analysis of the factors involved in cell cycle control. Results: Binding of HL60 to FN via a4b1 and a5b1 integrins exerted a CAM-DR phenotype, which shows resistance to apoptosis triggered by doxorubicin. FN-adherent HL60 cells accumulated in the G0/G1 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 G0/G1 cell cycle checkpoint showed that CAM-DR phenotype might be regulated mainly by p21waf/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.

Anahtar Kelimeler:

Apoptosis, CAM-DR, fibronectin, cell cycle

Adhesion of Beta1 Integrin to Fibronectin Regulates CAM-DR Phenotype via p21WAF1/cip1 in HL60 Acute Myeloid Leukemia (AML) Cells

Keywords:

Apoptosis, CAM-DR, fibronectin, cell cycle,

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