DUAL REGULATION OF BETA-LACTOGLOBULIN HUMAN SERUM-ALBUMIN GENE-EXPRESSION BY THE EXTRACELLULAR-MATRIX IN MAMMARY CELLS FROM TRANSGENIC MICE

Mammary explants and epithelial cell cultures from transgenic mice car rying the human serum albumin (HSA) gene or minigenes behind the regul atory sequences of the ovine beta-lactoglobulin gene were analyzed. Pr eviously we demonstrated that mammary explants from virgin female tran sgenic mice synthesize and secrete high levels of HSA during the first day in culture. Here we present a detailed analysis of endogenous and transgene expression during the first 20 h of mammary explant culture s. We show that HSA genes as well as endogenous milk protein genes are rapidly induced upon explantation. Unexpectedly, HSA was synthesized also in mammary explants from strains that do not secrete HSA into the milk, indicating the existence of a cryptic potential to express the transgene. Histological examination revealed that some luminal epithel ial cells detached from the underlying extracellular matrix (ECM) soon after explantation. Epithelial cell cultures from nonsecreting strain s grown on plastic rapidly induced transgene expression and secreted h igher levels of HSA into the medium compared to cells grown on collage n. These results suggest that tissue organization and most likely the interaction of epithelial cells with the ECM are intimately involved i n the control of HSA transgene expression. (C) 1996 Academic Press, In c.