Functional role of alpha4beta1 and alpha5beta1 integrin fibronectin receptors expressed on adriamycin-resistant MCF-7 human mammary carcinoma cells.
Cytofluorimetric and reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that adriamycin-resistant (ADRR), but not sensitive (WT), MCF-7 human mammary carcinoma cell lines express alpha4beta1 and alpha5beta1 integrins. ADR(R) cells adhere to fibronectin (FN), and only alpha5beta1 is involved in cell adhesion to this glycoprotein, while alpha4beta1 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 alpha5beta1, 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 alpha5beta1 on the resistant cells enables them to draw advantage from FN for both cell growth and survival.
Nista
A
A
Laboratory of Pathophysiology, Regina Elena Cancer Institute, Rome, Italy. nista@crs.ifo.it
Leonetti
C
C
Bernardini
G
G
Mattioni
M
M
Santoni
A
A
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism* / Q000502:physiology; D016133:Polymerase Chain Reaction; D017469:Receptors, Fibronectin / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology
D019012:Integrin beta1; D017469:Receptors, Fibronectin; D019010:Vascular Cell Adhesion Molecule-1; D004317:Doxorubicin