Studies of the regulation of the mouse carboxyl ester lipase gene in mammary gland

The lactating mammary gland and pancreas of mouse constitute the main tissu es for synthesis and secretion of a bile-salt-stimulated lipase called carb oxyl ester lipase (CEL). In this paper we have analysed the endogenous CEL gene expression in mammary gland. It is shown that the gene is expressed at day 14 of pregnancy, which is synchronous with that of the whey acidic pro tein (WAP) gene. Even though the CEL and WAP genes are induced at the same time during mammary gland differentiation, their regulation is different wi th respect to dependence on lactogenic hormones. The high induction of the WAP gene expression due to the activation of signal transducer and activato r of transcription (STAT)5 by prolactin has not been observed for the CEL g ene, even though it has been demonstrated that both STAT5 isoforms interact with one of the gamma-interferon activation sequence sites in the promoter of the CEL gene. Hence we have demonstrated that the prolactin/STAT5 signa l is not involved in a general and significant activation of 'milk genes'. Instead of a direct effect of the lactogenic hormones, the up-regulation of the CEL gene is correlated with an increase in the number of differentiate d epithelial cells. Furthermore, promoter studies using the mammary-gland-d erived cell line, HC11, show that a major positive element in the CEL gene promoter interacts with a member(s) of the CCAAT-binding transcription fact or/nuclear factor 1 family, binding to a palindromic site. Binding of this factor(s) is important for the tissue-specific activation of the CEL gene i n the mammary gland, because no activation by this factor(s) was seen in ce lls of pancreatic origin.