Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation

Overexpression of the receptor tyrosine kinase ErbB2/HER2/Neu (ErbB2) occur s in 15-40% of human breast cancers. To determine the function of ErbB2 sig naling during normal mouse mammary gland development, me expressed a carbox yl-terminal truncated dominant negative allele of ErbB2 (ErbB2 Delta IC) in the developing mouse mammary gland. Despite ErbB2 Delta IC expression with in mammary glands of pubescent virgin and pregnant mice, a phenotype was no t observed until late in pregnancy. At 1 day post-partum, lactationally act ive, distended lobuloalveoli failed to form. This phenotype was exaggerated in multiparous females expressing ErbB2 Delta IC. Immunohistochemical stai ning for ErbB2 Delta IC revealed a concordance between high levels of ErbB2 Delta IC protein expression and the absence of lactational products within the lumens of ErbB2 Delta IC stained lobuloalveoli. These results demonstr ate that ErbB2 signaling is required for proper mammary development and lac tation at parturition.