BETA-LACTOGLOBULIN HUMAN SERUM-ALBUMIN FUSION GENES DO NOT RESPOND ACCURATELY TO SIGNALS FROM THE EXTRACELLULAR-MATRIX IN MAMMARY EPITHELIAL-CELLS FROM TRANSGENIC MICE/

Mammary epithelial cell cultures from transgenic mice carrying the hum an serum albumin (HSA) gene or minigenes behind the regulatory sequenc es of the ovine beta-lactoglobulin gene were analyzed. Previously, we demonstrated that non-HSA-secreting transgenic strains retain the pote ntial to express the HSA transgene in vitro and that mammary epithelia l cell cultures from non-HSA-secreting strains express higher levels o f HSA when grown on tissue culture plastic than they do when grown on collagen. in this study we studied the expression of BLG/HSA fusion ge nes in epithelial cell cultures of additional transgenic strains and a dditional substrata. Our results show that: (1) The BLG/HSA fusion gen e in only one of seven HSA-secreting or nonsecreting transgenic strain s tested accurately responded to signals from the EH matrix; (2) HSA D NA sequences dominantly affected the activity of BLG as well as the wh ey acidic protein promoters; and (3) HGF/SF induced both milk proteins and HSA gene expression. These results suggest that the response to t he extra cellular matrix (ECM) plays a key role in the expression of B LG/HSA fusion genes and that the function of the regulatory elements w ithin the promoter regions of milk protein genes involved in response to the ECM, in developmental and in tissue specificity, very much depe nd on the downstream gene sequences. (C) 1996 Academic Press, Inc.