RELAXIN INFLUENCES GROWTH, DIFFERENTIATION AND CELL-CELL ADHESION OF HUMAN BREAST-CANCER CELLS IN CULTURE

The effects of differentiation concentrations of relaxin (RLX) on grow th and differentiation of a human breast-cancer cell line (MCF-7) have been studied after various times of exposure. The cells were cultured for 4 and 7 days in the absence (control) and the presence of highly purified porcine RLX at concentrations of 10(-9) M and 10(-6) M. (H-3) -Thymidine uptake assay was used to evaluate cell proliferation. Elect ron microscopy and immunocytochemistry for the cell-cell adhesion mole cule E-cadherin were carried out to evaluate cell differentiation. Ana lysis of DNA changes associated with apoptosis was performed to clarif y whether RLX induces active cell death in the MCF-7 cells. The findin gs obtained show that RLX, when applied at micromolar concentrations, or even at nanomolar concentrations for long exposure times, suppresse s proliferation, stimulates differentiation, and enhances expression o f the surface molecule E-cadherin. Growth inhibition is not accompanie d by apoptosis. The results of this study show that RLX can be recogni zed as a novel agent active in influencing growth and differentiation of MCF-7 breast-cancer cells. When applied at appropriate concentratio ns and exposure times, the peptide has a growth-inhibitory action, thu s reversing the growth-stimulatory effect exerted at low concentration s for short exposure times, and promotes differentiation and cell-cell adhesion. These last-mentioned properties might result in a decrease in invasiveness of breast adenocarcinoma cells. (C) 1994 Wiley-Liss, I nc.