EXPRESSION OF ANNEXIN-VI IN A431 CARCINOMA-CELLS SUPPRESSES PROLIFERATION - A POSSIBLE ROLE FOR ANNEXIN-VI IN CELL-GROWTH REGULATION

Human A431 cells exhibit many characteristics typical of transformed c ells, such as lack of contact inhibition and reduced growth factor req uirement. We have used these cells as a model for the study of annexin VI function, since they do not normally express this protein. In this study we isolated two stably transfected clones, both of which were f ound to express annexin Vi at physiological levels, and examined vario us growth parameters associated with the transformed phenotype. In low serum, normal A431 cells had doubling times similar to those observed in high serum. However, although the annexin VI transfectants grew on ly slightly more slowly than controls in high serum, their doubling ti me was significantly increased in low serum. Moreover, in low serum th e annexin VI transfectants stopped proliferating after reaching conflu ence, indicating contact inhibition. Fluorescence activated cell sorti ng analysis revealed that the annexin VI+ cells were growth arrested i n the G(1) phase of the cell cycle when cultured in low serum, whereas annexin VI- clones exhibited the same proportion of mitotic cells in both low and high serum. Thus, expression of annexin VI in a heterolog ous cell line has a moderating influence on cell proliferation suggest ing a possible role for annexin VI in cell growth regulation.