THE EPITHELIUM-SPECIFIC ETS TRANSCRIPTION FACTOR ESX IS ASSOCIATED WITH MAMMARY-GLAND DEVELOPMENT AND INVOLUTION

To study mammary gland expression of the epithelium-restricted Ets fac tor, ESX, mouse cDNA and genomic sequences were cloned and a similar t o 350 bp proximal promoter region with >80% mouse-human homology was i dentified that mediates ESX induction by serum, heregulin (HRG)I or ep idermal growth factor (EGF). ESX mRNA expression progressively increas es during embryonic mouse development from day 7 and is detectable in virgin mammary glands; it shows little if any change during pregnancy, then declines to barely detectable levels after 3 days of lactation. Similarly, cultured HC11 cells from midpregnant mouse mammary epitheli um show an increase in ESX expression upon reaching lactogenic compete ncy (in the presence of EGF or HRG), with a decline to barely detectab le levels upon exposure to lactogenic hormones that induce milk protei n (beta-casein) expression. In contrast, involuting mouse and rat mamm ary glands show maximal ESX expression. High ESX levels are also seen in the involuting ventral prostate gland of rats. These findings, incl uding the persistence of up-regulated ESX in fully regressed mammary g lands, suggest that ESX expression can be induced by soluble growth fa ctors and is maximally up-regulated in those partially com mitted epit helial cells destined to survive both the apoptotic and remodeling pha ses of glandular involution.