INHIBITORY EFFECTS OF ACTIVIN ON THE GROWTH AND MORPHOGENESIS OF PRIMARY AND TRANSFORMED MAMMARY EPITHELIAL-CELLS

Activin is a member of the transforming growth factor beta superfamily , which is known to have activities involved in regulating differentia tion and development. By using reverse transcription-PCR analysis on i mmunoaffinity-purified human breast cells, we have found that activin beta a and activin type II receptor are expressed by myoepithelial cel ls, whereas no expression was detected in other breast cell types. In examining 15 breast cell lines, we have found only four (HBL-100, MCF1 0-A, PMC-42, and BT 20) to be positive for activin beta a mRNA, wherea s all expressed the activin type II receptor, Furthermore, we have fou nd activin A to be a potent growth inhibitor of MCF-7 cells (at 2 ng/m l), where it causes an arrest in G(1). Activin A does not appear to ha ve an effect on the cell cycle of primary myoepithelial or luminal cel ls. However, we demonstrate that activin is an inhibitor of tubule for mation by human mammary organoids in vitro. These are the first observ ations of activin and activin receptor in the normal human breast and in human breast cell lines and suggest a role for activin in mammary c ell growth and morphogenesis.