The epithelium‐specific Ets transcription factor ESX is associated with mammary gland development and involution

• Published in: The FASEB journal Vol. 12; no. 14; pp. 1541 - 1550
• Main Authors: Neve, R., Chang, C.-H., Scott, G. K., Wong, A., Friis, R. R., Hynes, N. E., Benz, C. C.
• Format: Journal Article
• Language: English
• Published: United States Federation of American Societies for Experimental Biology 01-11-1998
• Subjects: Amino Acid Sequence; Animals; Base Sequence; DNA, Complementary; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epithelium - metabolism; ESX expression and mammary gland differentiation; ESX promoter; Ets family; Female; Humans; Mammary Glands, Animal - growth & development; Mammary Glands, Animal - metabolism; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Pregnancy; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ets; Rats; Rats, Sprague-Dawley; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.12.14.1541

To study mammary gland expression of the epithelium‐restricted Ets factor, ESX, mouse cDNA and genomic sequences were cloned and a ∼350 bp proximal promoter region with >80% mouse–human homology was identified that mediates ESX induction by serum, heregulin (HRG), or epidermal growth factor (EGF). ESX mRNA expression progressively increases 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 epithelium show an increase in ESX expression upon reaching lactogenic competency (in the presence of EGF or HRG), with a decline to barely detectable levels upon exposure to lactogenic hormones that induce milk protein (β‐casein) expression. In contrast, involuting mouse and rat mammary glands show maximal ESX expression. High ESX levels are also seen in the involuting ventral prostate gland of rats. These findings, including the persistence of up‐regulated ESX in fully regressed mammary glands, suggest that ESX expression can be induced by soluble growth factors and is maximally up‐regulated in those partially committed epithelial cells destined to survive both the apoptotic and remodeling phases of glandular involution.— Neve, R., Chang, C.‐H., Scott, G. K., Wong, A., Friis, R. R., Hynes, N. E., Benz, C. C. The epithelium‐ specific Ets transcription factor ESX is associated with mammary gland development and involution. FASEB J. 12, 1541–1550 (1998)