Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland

Nicholas J. Kenney, Gilbert H. Smith, Karen Rosenberg, Mary Lou Cutler, Robert B. Dickson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


As the juvenile mouse mammary gland matures, it undergoes extensive epithelial proliferation, leading to a network of ductal branching that transverses the organ. Recent evidence suggests that the epidermal growth factor-related peptide amphiregulin (AR) may play multiple roles in the proliferation, differentiation, and neoplastic conversion of the mouse mammary gland. Using a dual approach of recombinant AR in slow-release pellets and retroviral expression of AR, we explored the roles of this growth factor in the mouse mammary gland in vivo. We first noted that recombinant AR can reestablish longitudinal ductal proliferation in growth quiescent mammary glands of ovariectomized mice. Furthermore, retrovitally transduced mammary transplants overexpressing AR developed into hyperplastic tertiary ducts and hyperplastic lobules with increased lateral branching, apparent 9 weeks after transplantation into cleared mammary fat pads. This is the first study to demonstrate that AR can reestablish the early developmental activity of ductal mammary epithelium and induce hyperplasia in vive. These data, coupled with previous findings that demonstrated nearly universal overexpression of AR in human breast cancer and rodent mammary tumorigenesis, suggest that AR may be an important intermediary in glandular maturation and early malignant progression.

Original languageEnglish
Pages (from-to)1769-1781
Number of pages13
JournalCell Growth and Differentiation
Issue number12
StatePublished - 1996
Externally publishedYes


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