| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B p50/p65 is regulated in the developing mammary gland and inhibits STAT5-mediated ß-casein gene expression
Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, A-6020 Innsbruck, Austria
1Correspondence: Institute f. Medizinische Chemie und Biochemie, Universität Innsbruck, Fritz Pregl-Str. 3, A-6020 Innsbruck, Austria. E-mail: Wolfgang.Doppler{at}uibk.ac.at osupersub
The NF-
B family of transcription factors regulates diverse cellular
functions such as immune response and cell growth and development, and
has been reported to be constitutively active in a variety of mammary
carcinoma cell lines. However, its role in normal mammary gland
development has not been addressed. In our study, we detected
developmentally regulated NF-B activity in the mammary gland of
mice. During pregnancy, DNA binding activity of NF-B p50/p65
increased until day 16 postcoitum and decreased with the onset of
lactation, most likely due to reduced p50 and p65 protein levels in the
nucleus. Cotransfection experiments performed with 293 cells revealed
an inhibition of the prolactin receptor/JAK2/STAT5 pathway by NF-B.
In HC11 cells, NF-B p50/p65 activity was inversely correlated with
prolactin-induced STAT5 tyrosine phosphorylation, expression of
endogenous ß-casein gene, and of a transfected ß-casein gene
promoter reporter construct. This indicates a negative cross talk
between NF-B and the prolactin receptor/JAK2/STAT5 activation
pathway, which occurs at the level of STAT5 tyrosine phosphorylation.
Our results provide evidence for a role of NF-B in normal mammary
gland development, and indicate its function as a negative regulator of
ß-casein gene expression during pregnancy by interfering with STAT5
tyrosine phosphorylation.—Geymayer, S., Doppler, W. Activation of
NF-B p50/p65 is regulated in the developing mammary gland and
inhibits STAT5-mediated ß-casein gene expression.
Key Words: TNF-
• prolactin • milk protein gene transcription • tyrosine phosphorylation
This article has been cited by other articles:
|
|
 |
|
  M. D. Buzzelli, M. Nagarajan, J. F. Radtka, M. L. Shumate, M. Navaratnarajah, C. H. Lang, and R. N. Cooney Nuclear Factor-{kappa}B Mediates the Inhibitory Effects of Tumor Necrosis Factor-{alpha} on Growth Hormone-Inducible Gene Expression in Liver Endocrinology, December 1, 2008; 149(12): 6378 - 6388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhu, C. Johnson, and M. Bakovic Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1 J. Lipid Res., October 1, 2008; 49(10): 2197 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
A. Zeold, M. Doleschall, M. C. Haffner, L. P. Capelo, J. Menyhert, Z. Liposits, W. S. da Silva, A. C. Bianco, I. Kacskovics, C. Fekete, et al. Characterization of the Nuclear Factor-{kappa}B Responsiveness of the Human dio2 Gene Endocrinology, September 1, 2006; 147(9): 4419 - 4429. [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. M. Johansson, M. Kannius-Janson, A. Gritli-Linde, G. Bjursell, and J. Nilsson Nuclear Factor 1-C2 Is Regulated by Prolactin and Shows a Distinct Expression Pattern in the Mouse Mammary Epithelial Cells during Development Mol. Endocrinol., April 1, 2005; 19(4): 992 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Murtagh, E. McArdle, E. Gilligan, L. Thornton, F. Furlong, and F. Martin Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling J. Cell Biol., July 5, 2004; 166(1): 133 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, H. Zhang, L. Lee, and M. M. Ip The Liver-Enriched Inhibitory Protein Isoform of CCAAT/Enhancer-Binding Protein {beta}, But Not Nuclear Factor-{kappa}B, Mediates the Transcriptional Inhibition of {beta}-Casein by Tumor Necrosis Factor-{alpha} Endocrinology, June 1, 2004; 145(6): 2833 - 2844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fekete, B. Gereben, M. Doleschall, J. W. Harney, J. M. Dora, A. C. Bianco, S. Sarkar, Z. Liposits, W. Rand, C. Emerson, et al. Lipopolysaccharide Induces Type 2 Iodothyronine Deiodinase in the Mediobasal Hypothalamus: Implications for the Nonthyroidal Illness Syndrome Endocrinology, April 1, 2004; 145(4): 1649 - 1655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Safieh-Garabedian, G M Mouneimne, W El-Jouni, M Khattar, and R Talhouk The effect of endotoxin on functional parameters of mammary CID-9 cells Reproduction, March 1, 2004; 127(3): 397 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Komine, T. Kuroishi, Y. Komine, K. Watanabe, J. Kobayashi, T. Yamaguchi, S.-i. Kamata, and K. Kumagai Induction of Nitric Oxide Production Mediated by Tumor Necrosis Factor Alpha on Staphylococcal Enterotoxin C-Stimulated Bovine Mammary Gland Cells Clin. Vaccine Immunol., January 1, 2004; 11(1): 203 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Paukku, J. Yang, and O. Silvennoinen Tudor and Nuclease-Like Domains Containing Protein p100 Function as Coactivators for Signal Transducer and Activator of Transcription 5 Mol. Endocrinol., September 1, 2003; 17(9): 1805 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Widschwendter, S. Tonko-Geymayer, T. Welte, G. Daxenbichler, C. Marth, and W. Doppler Prognostic Significance of Signal Transducer and Activator of Transcription 1 Activation in Breast Cancer Clin. Cancer Res., October 1, 2002; 8(10): 3065 - 3074. [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]
|
|
|
|
|
|
Y. E. Timsit and D. S. Riddick Stimulation of Hepatic Signal Transducer and Activator of Transcription 5b by GH Is Not Altered by 3-Methylcholanthrene Endocrinology, September 1, 2002; 143(9): 3284 - 3294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-Y. Yu-Lee Prolactin Modulation of Immune and Inflammatory Responses Recent Prog. Horm. Res., January 1, 2002; 57(1): 435 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Teixeira, S. Maheswaran, and P. K. Donahoe Mullerian Inhibiting Substance: An Instructive Developmental Hormone with Diagnostic and Possible Therapeutic Applications Endocr. Rev., October 1, 2001; 22(5): 657 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Shea-Eaton, P.-P. H. Lee, and M. M. Ip Regulation of Milk Protein Gene Expression in Normal Mammary Epithelial Cells by Tumor Necrosis Factor Endocrinology, June 1, 2001; 142(6): 2558 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Segev, Y. Hoshiya, A. E. Stephen, M. Hoshiya, T. T. Tran, D. T. MacLaughlin, P. K. Donahoe, and S. Maheswaran Mullerian Inhibiting Substance Regulates NFkappa B Signaling and Growth of Mammary Epithelial Cells in Vivo J. Biol. Chem., July 13, 2001; 276(29): 26799 - 26806. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
