QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brantley, D. M. Articles by Yull, F. E. Search for Related Content PubMed PubMed Citation Articles by Brantley, D. M. Articles by Yull, F. E.

Vol. 12, Issue 5, 1445-1455, May 2001

Nuclear Factor-B (NF-B) Regulates Proliferation and Branching in Mouse Mammary Epithelium

Dana M. Brantley,^* Chih-Li Chen, Rebecca S. Muraoka,^§ Paul B. Bushdid, Jonathan L. Bradberry, Frances Kittrell, Daniel Medina, Lynn M. Matrisian,^*¶#@ Lawrence D. Kerr,^*¶** and Fiona E. Yull^¶#

 Departments of Microbiology and Immunology,  ^*Cell Biology,  ^§ Hematology and Oncology, and  ^#Cancer Biology, Vanderbilt University School of Medicine and  ^¶Vanderbilt Ingram Cancer Center, Nashville, Tennessee 37232-2175;  MD Anderson Cancer Center, Baylor College of Medicine, Houston, Texas 77030; and  ^**Executive Office of the President, Office of Science and Technology Policy, Washington, DC 20500

The nuclear factor-B (NF-B) family of transcription factors has been shown to regulate proliferation in several cell types. Although recent studies have demonstrated aberrant expression or activity of NF-B in human breast cancer cell lines and tumors, little is known regarding the precise role of NF-B in normal proliferation and development of the mammary epithelium. We investigated the function of NF-B during murine early postnatal mammary gland development by observing the consequences of increased NF-B activity in mouse mammary epithelium lacking the gene encoding IB, a major inhibitor of NF-B. Mammary tissue containing epithelium from inhibitor B (IB)-deficient female donors was transplanted into the gland-free mammary stroma of wild-type mice, resulting in an increase in lateral ductal branching and pervasive intraductal hyperplasia. A two- to threefold increase in epithelial cell number was observed in IB-deficient epithelium compared with controls. Epithelial cell proliferation was strikingly increased in IB-deficient epithelium, and no alteration in apoptosis was detected. The extracellular matrix adjacent to IB-deficient epithelium was reduced. Consistent with in vivo data, a fourfold increase in epithelial branching was also observed in purified IB-deficient primary epithelial cells in three-dimensional culture. These data demonstrate that NF-B positively regulates mammary epithelial proliferation, branching, and functions in maintenance of normal epithelial architecture during early postnatal development.

---

These authors contributed equally to this work.

^@ Corresponding author. E-mail address: Lynn.Matrisian{at}mcmail.vanderbilt.edu.

---

Molecular Biology of the Cell
Vol. 12, 1445-1455, May 2001
Copyright © 2001 by The American Society for Cell Biology

This article has been cited by other articles:

				L. Connelly, C. Robinson-Benion, M. Chont, L. Saint-Jean, H. Li, V. V. Polosukhin, T. S. Blackwell, and F. E. Yull A Transgenic Model Reveals Important Roles for the NF-{kappa}B Alternative Pathway (p100/p52) in Mammary Development and Links to Tumorigenesis J. Biol. Chem., March 30, 2007; 282(13): 10028 - 10035. [Abstract] [Full Text] [PDF]

				J. Zhang, M. A. Warren, S. F. Shoemaker, and M. M. Ip NF{kappa}B1/p50 Is Not Required for Tumor Necrosis Factor-Stimulated Growth of Primary Mammary Epithelial Cells: Implications for NF{kappa}B2/p52 and RelB Endocrinology, January 1, 2007; 148(1): 268 - 278. [Abstract] [Full Text] [PDF]

				D. M. Brantley-Sieders, W. B. Fang, Y. Hwang, D. Hicks, and J. Chen Ephrin-A1 Facilitates Mammary Tumor Metastasis through an Angiogenesis-Dependent Mechanism Mediated by EphA Receptor and Vascular Endothelial Growth Factor in Mice Cancer Res., November 1, 2006; 66(21): 10315 - 10324. [Abstract] [Full Text] [PDF]

				N.-S. Kim, H.-J. Kim, B.-K. Koo, M.-C. Kwon, Y.-W. Kim, Y. Cho, Y. Yokota, J. M. Penninger, and Y.-Y. Kong Receptor Activator of NF-{kappa}B Ligand Regulates the Proliferation of Mammary Epithelial Cells via Id2 Mol. Cell. Biol., February 1, 2006; 26(3): 1002 - 1013. [Abstract] [Full Text] [PDF]

				E. G. Demicco, K. T. Kavanagh, R. Romieu-Mourez, X. Wang, S. R. Shin, E. Landesman-Bollag, D. C. Seldin, and G. E. Sonenshein RelB/p52 NF-{kappa}B Complexes Rescue an Early Delay in Mammary Gland Development in Transgenic Mice with Targeted Superrepressor I{kappa}B-{alpha} Expression and Promote Carcinogenesis of the Mammary Gland Mol. Cell. Biol., November 15, 2005; 25(22): 10136 - 10147. [Abstract] [Full Text] [PDF]

				N. Currier, S. E. Solomon, E. G. Demicco, D. L. F. Chang, M. Farago, H. Ying, I. Dominguez, G. E. Sonenshein, R. D. Cardiff, Z.-X. J. Xiao, et al. Oncogenic Signaling Pathways Activated in DMBA-Induced Mouse Mammary Tumors Toxicol Pathol, October 1, 2005; 33(6): 726 - 737. [Abstract] [Full Text] [PDF]

				Y. Kudo, D. Guardavaccaro, P. G. Santamaria, R. Koyama-Nasu, E. Latres, R. Bronson, L. Yamasaki, and M. Pagano Role of F-Box Protein {beta}Trcp1 in Mammary Gland Development and Tumorigenesis Mol. Cell. Biol., September 15, 2004; 24(18): 8184 - 8194. [Abstract] [Full Text] [PDF]

				E. Saez, J. Rosenfeld, A. Livolsi, P. Olson, E. Lombardo, M. Nelson, E. Banayo, R. D. Cardiff, J. C. Izpisua-Belmonte, and R. M. Evans PPAR{gamma} signaling exacerbates mammary gland tumor development Genes & Dev., March 1, 2004; 18(5): 528 - 540. [Abstract] [Full Text] [PDF]

				S. Srivastava, M. Matsuda, Z. Hou, J. P. Bailey, R. Kitazawa, M. P. Herbst, and N. D. Horseman Receptor Activator of NF-{kappa}B Ligand Induction via Jak2 and Stat5a in Mammary Epithelial Cells J. Biol. Chem., November 14, 2003; 278(46): 46171 - 46178. [Abstract] [Full Text] [PDF]

				R. Romieu-Mourez, D. W. Kim, S. M. Shin, E. G. Demicco, E. Landesman-Bollag, D. C. Seldin, R. D. Cardiff, and G. E. Sonenshein Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors Mol. Cell. Biol., August 15, 2003; 23(16): 5738 - 5754. [Abstract] [Full Text] [PDF]

				J. A. Choudhury, C. L. Russell, S. Randhawa, L. S. Young, D. H. Adams, and S. C. Afford Differential Induction of Nuclear Factor-kappa B and Activator Protein-1 Activity after CD40 Ligation Is Associated with Primary Human Hepatocyte Apoptosis or Intrahepatic Endothelial Cell Proliferation Mol. Biol. Cell, April 1, 2003; 14(4): 1334 - 1345. [Abstract] [Full Text] [PDF]

				M. M. Faraldo, M.-A. Deugnier, S. Tlouzeau, J. P. Thiery, and M. A. Glukhova Perturbation of beta 1-Integrin Function in Involuting Mammary Gland Results in Premature Dedifferentiation of Secretory Epithelial Cells Mol. Biol. Cell, October 1, 2002; 13(10): 3521 - 3531. [Abstract] [Full Text] [PDF]