QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 28 September 2005
doi: 10.1242/dev.02050

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02050v1 132/21/4675    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Thangaraju, M. Articles by Sterneck, E. Search for Related Content PubMed PubMed Citation Articles by Thangaraju, M. Articles by Sterneck, E.

C/EBP is a crucial regulator of pro-apoptotic gene expression during mammary gland involution

Muthusamy Thangaraju^1,*, Martina Rudelius², Brian Bierie^3,, Mark Raffeld², Shikha Sharan¹, Lothar Hennighausen³, A-Mei Huang^1, and Esta Sterneck^1,

¹ Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA
² Laboratory of Pathology, National Cancer Institute, National Institute of Health, Bethesda MD 20892, USA
³ Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD 20892, USA

Author for correspondence (e-mail: sterneck{at}ncifcrf.gov)

Accepted 19 August 2005

The STAT3 transcription factor is an important initiator of mammary gland involution in the mouse. This work shows that the STAT3 target gene CCAAT/enhancer binding protein delta (C/EBP) is a crucial mediator of pro-apoptotic gene expression events in mammary epithelial cells. In the absence of C/EBP, involution is delayed, the pro-apoptotic genes encoding p53, BAK, IGFBP5 and SGP2/clusterin are not activated, while the anti-apoptotic genes coding for BFL1 and Cyclin D1 are not repressed. Consequently, p53 targets such as survivin, BRCA1, BRCA2 and BAX are not regulated appropriately and protease activation is delayed. Furthermore, expression of MMP3 and C/EBP during the second phase of involution is perturbed in the absence of C/EBP. In HC11 cells, C/EBP alone is sufficient to induce IGFBP5 and SGP2. It also suppresses Cyclin D1 expression and cooperates with p53 to elicit apoptosis. This study places C/EBP between STAT3 and several pro- and anti-apoptotic genes promoting the physiological cell death response in epithelial cells at the onset of mammary gland involution.

Key words: Mammary gland, Involution, C/EBP, Apoptosis, Mouse

This article has been cited by other articles:

				P. G. Tiffen, N. Omidvar, N. Marquez-Almuina, D. Croston, C. J. Watson, and R. W. E. Clarkson A Dual Role for Oncostatin M Signaling in the Differentiation and Death of Mammary Epithelial Cells in Vivo Mol. Endocrinol., December 1, 2008; 22(12): 2677 - 2688. [Abstract] [Full Text] [PDF]

				J. S. Bates, D. B. Petry, J. Eudy, L. Bough, and R. K. Johnson Differential expression in lung and bronchial lymph node of pigs with high and low responses to infection with porcine reproductive and respiratory syndrome virus J Anim Sci, December 1, 2008; 86(12): 3279 - 3289. [Abstract] [Full Text] [PDF]

				C.-Y. Ko, H.-C. Hsu, M.-R. Shen, W.-C. Chang, and J.-M. Wang Epigenetic Silencing of CCAAT/Enhancer-binding Protein {delta} Activity by YY1/Polycomb Group/DNA Methyltransferase Complex J. Biol. Chem., November 7, 2008; 283(45): 30919 - 30932. [Abstract] [Full Text] [PDF]

				H. Frank, N. Groger, M. Diener, C. Becker, T. Braun, and T. Boettger Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice J. Biol. Chem., September 5, 2008; 283(36): 24729 - 24737. [Abstract] [Full Text] [PDF]

				S. H. Slofstra, A. P. Groot, M. H. P. Obdeijn, P. H. Reitsma, H. ten Cate, and C. A. Spek Gene Expression Profiling Identifies C/EBP{delta} as a Candidate Regulator of Endotoxin-induced Disseminated Intravascular Coagulation Am. J. Respir. Crit. Care Med., September 15, 2007; 176(6): 602 - 609. [Abstract] [Full Text] [PDF]

				M. M. McKay and D. K. Morrison Caspase-dependent Cleavage Disrupts the ERK Cascade Scaffolding Function of KSR1 J. Biol. Chem., September 7, 2007; 282(36): 26225 - 26234. [Abstract] [Full Text] [PDF]

				T. McArthur and A. Ohtoshi A Brain-Specific Homeobox Gene, Bsx, Is Essential for Proper Postnatal Growth and Nursing Mol. Cell. Biol., July 15, 2007; 27(14): 5120 - 5127. [Abstract] [Full Text] [PDF]

				M. C. Rudolph, J. L. McManaman, T. Phang, T. Russell, D. J. Kominsky, N. J. Serkova, T. Stein, S. M. Anderson, and M. C. Neville Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine Physiol Genomics, February 12, 2007; 28(3): 323 - 336. [Abstract] [Full Text] [PDF]

				M. Thangaraju, S. Ananth, P. M. Martin, P. Roon, S. B. Smith, E. Sterneck, P. D. Prasad, and V. Ganapathy c/ebp{delta} Null Mouse as a Model for the Double Knock-out of slc5a8 and slc5a12 in Kidney J. Biol. Chem., September 15, 2006; 281(37): 26769 - 26773. [Abstract] [Full Text] [PDF]

				R. W. E. Clarkson, M. P. Boland, E. A. Kritikou, J. M. Lee, T. C. Freeman, P. G. Tiffen, and C. J. Watson The Genes Induced by Signal Transducer and Activators of Transcription (STAT)3 and STAT5 in Mammary Epithelial Cells Define the Roles of these STATs in Mammary Development Mol. Endocrinol., March 1, 2006; 20(3): 675 - 685. [Abstract] [Full Text] [PDF]