THE ROLE OF MYOEPITHELIAL-DERIVED GROWTH-FACTORS IN THE HUMAN BREAST

We have studied separated human breast epithelial and myoepithelial ce lls for the presence of basic fibroblast growth factor (FGF2) and its receptors and for the effects of FGF2 on the proliferation of both cel l types. We have also studied the role of activin and its receptor in controlling cell proliferation. Our results indicated that these cell types differ markedly in synthesis and response to FGF2 and activin an d in their receptor content. FGF2 had no effect on the proliferation o f myoepithelial cells but promoted the survival of the separated epith elial cells. Immunostainable FGF receptors 1 and 4 were present in epi thelial cells and to a lesser extent in myoepithelial cells. These res ults indicated that myoepithelial-derived FGF2 may be important in con trolling epithelial cell survival and that differential receptor expre ssion could control FGF2 action in these different cell types. We foun d that activin beta-a and activin type II receptor are expressed by my oepithelial cells, whereas no expression was detected in other breast cell types. In examining 15 breast cell lines, we found only four (HBL -100, MCF-10A, PMC-42 and BT-20) to be positive for activin beta-a mRN A, whereas all expressed the activin type II receptor. Furthermore, we have found activin A to be a potent growth inhibitor of MCF-7 cells w here it causes an arrest in G(1). Activin A does not appear to have an effect on the cell cycle of primary myoepithelial or luminal cells. H owever, we have demonstrated that activin is an inhibitor of tubule fo rmation by human mammary organoids in vitro.