|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 9, 6191-6199, March 2, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Division of Tumor Biology, Netherlands Cancer Institute,
Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
The mucin-like glycoprotein episialin (MUC1) is
highly overproduced by a number of human carcinomas. We have shown
previously in a variety of mammalian cell lines that overexpression of
this very large transmembrane molecule diminishes cellular adhesion, suggesting that episialin/MUC1 overexpression may play an important role in tumor invasion and metastasis. By using in situ
hybridization, we show here that episialin/MUC1 mRNA expression can
be increased more than 10-fold in breast carcinoma cells relative to
the expression in adjacent normal breast epithelium. In search of the
molecular mechanism of this overexpression, we observed that the
episialin/MUC1 promoter contains a candidate binding site
for transcription factors of the STAT family ~500 base pairs upstream
of the transcription start site. Cytokines and/or growth factors such
as interleukin-6 or interferon-
A STAT-responsive Element in the Promoter of the
Episialin/MUC1 Gene Is Involved in Its Overexpression in
Carcinoma Cells*
§,¶,
can activate STATs. In the human
breast carcinoma cell line T47D, both compounds are able to stimulate
transcription of a luciferase reporter gene under the control of a
750-base pair MUC1 promoter fragment proximal to the
transcription start site. The observed increase is entirely mediated by
the single STAT-binding site, since mutation of this site abolishes
stimulation of the reporter by interleukin-6 and interferon-. In
addition, mutation of the STAT site also decreased the promoter
activity in nonstimulated T47D cells, suggesting that the STAT-binding site is among the elements that are involved in the overexpression of
MUC1 in tumor cells.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Both authors contributed equally to this work.
§
Supported by NCI Grant 1R01 CA79580-01 from the National Institutes
of Health.
¶
Supported by Grant 93-523 of the Dutch Cancer Society.
To whom correspondence should be addressed. Tel.:
31-20-5122018; Fax: 31-20-5122029; E-mail: jhi@nki.nl.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Maher and S. Wilkie CAR Mechanics: Driving T Cells into the MUC of Cancer Cancer Res., June 1, 2009; 69(11): 4559 - 4562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Pitroda, N. N. Khodarev, M. A. Beckett, D. W. Kufe, and R. R. Weichselbaum From the Cover: MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment PNAS, April 7, 2009; 106(14): 5837 - 5841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wilkie, G. Picco, J. Foster, D. M. Davies, S. Julien, L. Cooper, S. Arif, S. J. Mather, J. Taylor-Papadimitriou, J. M. Burchell, et al. Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor J. Immunol., April 1, 2008; 180(7): 4901 - 4909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kuwahara, E. P. Lillehoj, T. Koga, Y. Isohama, T. Miyata, and K. C. Kim The Signaling Pathway Involved in Neutrophil Elastase Stimulated MUC1 Transcription Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 691 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Brayman, N. Dharmaraj, E. Lagow, and D. D. Carson MUC1 Expression Is Repressed by Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y Mol. Endocrinol., November 1, 2007; 21(11): 2725 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Koga, I. Kuwahara, E. P. Lillehoj, W. Lu, T. Miyata, Y. Isohama, and K. C. Kim TNF-{alpha} induces MUC1 gene transcription in lung epithelial cells: its signaling pathway and biological implication Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L693 - L701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Beatty, S. E. Plevy, A. R. Sepulveda, and O. J. Finn Cutting Edge: Transgenic Expression of Human MUC1 in IL-10-/- Mice Accelerates Inflammatory Bowel Disease and Progression to Colon Cancer J. Immunol., July 15, 2007; 179(2): 735 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Siragusa, M. Zerilli, F. Iovino, M. G. Francipane, Y. Lombardo, L. Ricci-Vitiani, G. Di Gesu, M. Todaro, R. De Maria, and G. Stassi MUC1 Oncoprotein Promotes Refractoriness to Chemotherapy in Thyroid Cancer Cells Cancer Res., June 1, 2007; 67(11): 5522 - 5530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kondo, T. Yoshizaki, N. Wakisaka, T. Horikawa, S. Murono, K. L. Jang, I. Joab, M. Furukawa, and J. S. Pagano MUC1 Induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of the Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling J. Virol., February 15, 2007; 81(4): 1554 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Brayman, J. Julian, B. Mulac-Jericevic, O. M. Conneely, D. P. Edwards, and D. D. Carson Progesterone Receptor Isoforms A and B Differentially Regulate MUC1 Expression in Uterine Epithelial Cells Mol. Endocrinol., October 1, 2006; 20(10): 2278 - 2291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kuwahara, E. P. Lillehoj, A. Hisatsune, W. Lu, Y. Isohama, T. Miyata, and K. C. Kim Neutrophil elastase stimulates MUC1 gene expression through increased Sp1 binding to the MUC1 promoter Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L355 - L362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Cramer, L. Titus-Ernstoff, J. R. McKolanis, W. R. Welch, A. F. Vitonis, R. S. Berkowitz, and O. J. Finn Conditions Associated with Antibodies Against the Tumor-Associated Antigen MUC1 and Their Relationship to Risk for Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1125 - 1131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-l. Yuan, Y.-j. Guan, L. Wang, W. Wei, A. B. Kane, and Y. E. Chin Central Role of the Threonine Residue within the p+1 Loop of Receptor Tyrosine Kinase in STAT3 Constitutive Phosphorylation in Metastatic Cancer Cells Mol. Cell. Biol., November 1, 2004; 24(21): 9390 - 9400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yin, Y. Li, J. Ren, H. Kuwahara, and D. Kufe Human MUC1 Carcinoma Antigen Regulates Intracellular Oxidant Levels and the Apoptotic Response to Oxidative Stress J. Biol. Chem., September 12, 2003; 278(37): 35458 - 35464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Z. Rassidakis, A. Goy, L. J. Medeiros, Y. Jiang, A. Thomaides, Y. Remache, F. Cabanillas, A. H. Sarris, and F. Gilles Prognostic Significance of MUC-1 Expression in Systemic Anaplastic Large Cell Lymphoma Clin. Cancer Res., June 1, 2003; 9(6): 2213 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Hinojosa-Kurtzberg, M. E. V. Johansson, C. S. Madsen, G. C. Hansson, and S. J. Gendler Novel MUC1 splice variants contribute to mucin overexpression in CFTR-deficient mice Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G853 - G862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. J. Lee, S. W. Hyun, A. Nandi, and K. C. Kim Transcriptional regulation of the hamster Muc1 gene: identification of a putative negative regulatory element Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L160 - L168. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |