Expression of c-myc is down-regulated as mouse mammary epithelial cells become confluent

We have investigated the expression profile of c-mye in the mammary gland, During pregnancy when the gland is actively growing c-myc mRNA was present, while in the differentiated lactating gland no c-myc mRNA was detected. This correspondence between the differentiation state and c-mye mRNA levels in the mouse mammary gland in viva was paralleled by HC11 mouse mammary epithelial cells in vitro. Firstly, the endogenous c-mye gene was suppressed in confluent compared to growing HC11 cells. in addition, treating the cells with lactogenic hormones did not induce c-myc expression. Secondly, a stably transfected c-myc-CAT reporter construct was similarly down-regulated, Furthermore, using this transfection model, we demonstrate that the mechanism(s) involved in regulating c-myc expression must act through the P1 and P2 core promoter and exon 1. Finally, we demonstrate that suppression of c-myc expression occurs when HC11 cells growth-arrest as they become confluent. (C) 1997 Academic Press.