Functional role of α4β1 and α5β1 integrin fibronectin receptors expressed on adriamycin-resistant MCF-7 human mammary carcinoma cells

Abstract

Cytofluorimetric and reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that adriamycin-resistant (ADR(R)), but not sensitive (WT), MCF-7 human mammary carcinoma cell lines express α4β1 and α5β1 integrins. ADR(R) cells adhere to fibronectin (FN), and only α5β1 is involved in cell adhesion to this glycoprotein, while α4β1 mediates cell binding to the cellular counter-receptor VCAM-1. Proliferation assays showed that FN, but not VCAM-1, delivers a mitogenic signal to quiescent ADR(R) MCF- 7 cells. The activating signal is mediated by α5β1, since cell proliferation is inhibited in the presence of RGD peptide or specific antibody. Cell cycle analysis demonstrated that cell/FN interaction induces the re-entry of ADR(R) MCF-7 into S phase, and prevents them from undergoing serum deprivation-induced apoptosis. Our data suggest that the presence of α5β1 on the resistant cells enables them to draw advantage from FN for both cell growth and survival.