Cell Growth & Differentiation, Vol 7, Issue 12 1769-1781, Copyright © 1996 by American Association of Cancer Research

ARTICLES

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

NJ Kenney, GH Smith, K Rosenberg, ML Cutler and RB Dickson
Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.

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, retrovirally 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 vivo. 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.

This article has been cited by other articles:

				M. Dahlhoff, A. Blutke, R. Wanke, E. Wolf, and M. R. Schneider In Vivo Evidence for Epidermal Growth Factor Receptor (EGFR)-mediated Release of Prolactin from the Pituitary Gland J. Biol. Chem., November 11, 2011; 286(45): 39297 - 39306. [Abstract] [Full Text] [PDF]

				L. K. Bade, J. E. Goldberg, H. A. DeHut, M. K. Hall, and K. L. Schwertfeger Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor J. Cell Sci., September 15, 2011; 124(18): 3106 - 3117. [Abstract] [Full Text] [PDF]

				L. Ciarloni, S. Mallepell, and C. Brisken Amphiregulin is an essential mediator of estrogen receptor {alpha} function in mammary gland development PNAS, March 27, 2007; 104(13): 5455 - 5460. [Abstract] [Full Text] [PDF]

				M. D. Sternlicht, S. W. Sunnarborg, H. Kouros-Mehr, Y. Yu, D. C. Lee, and Z. Werb Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin Development, September 1, 2005; 132(17): 3923 - 3933. [Abstract] [Full Text] [PDF]

				S.-H. Chang, Y. Ai, R. M. Breyer, T. F. Lane, and T. Hla The Prostaglandin E2 Receptor EP2 Is Required for Cyclooxygenase 2-Mediated Mammary Hyperplasia Cancer Res., June 1, 2005; 65(11): 4496 - 4499. [Abstract] [Full Text] [PDF]

				A. J. Jackson-Fisher, G. Bellinger, R. Ramabhadran, J. K. Morris, K.-F. Lee, and D. F. Stern ErbB2 is required for ductal morphogenesis of the mammary gland PNAS, December 7, 2004; 101(49): 17138 - 17143. [Abstract] [Full Text] [PDF]

				F. E. Jones, T. Welte, X.-Y. Fu, and D. F. Stern Erbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation J. Cell Biol., October 4, 1999; 147(1): 77 - 88. [Abstract] [Full Text] [PDF]

				N. Luetteke, T. Qiu, S. Fenton, K. Troyer, R. Riedel, A Chang, and D. Lee Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development Development, January 6, 1999; 126(12): 2739 - 2750. [Abstract] [PDF]