HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 13, 12093-12101, March 26, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/13/12093    most recent M311532200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bateman, N. W. Articles by Black, A. R. Search for Related Content PubMed PubMed Citation Articles by Bateman, N. W. Articles by Black, A. R. Social Bookmarking                      What's this?

Intestinal Tumor Progression Is Associated with Altered Function of KLF5^*

Nicholas W. Bateman, Dongfeng Tan, Richard G. Pestell¶, Jennifer D. Black, and Adrian R. Black||

From the Departments of Pharmacology and Therapeutics and Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263 and the ^¶Department of Oncology, Lombardi Cancer Center, Georgetown Medical Center, Washington, D. C. 20057

Krüppel-like transcription factors have been linked to cell growth regulation and tumorigenesis in a number of systems. In the intestinal epithelium, expression of KLF5 (IKLF/BTEB2) is limited to proliferating crypt cells, indicating a growth-promoting role. Consistent with this role, we demonstrate that expression of KLF5 in non-transformed intestinal epithelial cells (ileal IEC-18 and Immorto-Min Colon Epithelial (IMCE) cells) enhances colony formation, cyclin D1 transcription, and cell growth. However, in contrast to these effects in non-transformed cells, KLF5 reduced colony number, failed to enhance cyclin D1 transcription, and was negatively correlated with cell growth in colon cancer cell lines. The relationship between tumor progression and KLF5 was further investigated using Ras-mediated transformation of IEC-18 and IMCE cells as syngeneic models. Ras-transformation recapitulated differences in the effects of KLF5 on cell growth and cyclin D1 transcription, providing a direct link between intestinal tumor progression and altered function of KLF5. Ras-transformation also markedly down-regulated KLF5; further analysis indicated that reduced expression of KLF5 mRNA and destabilization of KLF5 protein occur in intestinal tumors. Reduced levels of KLF5 mRNA were also detected in APC^min mouse and human familial adenomatous polyposis adenomas compared with normal crypt epithelium, indicating that down-regulation of KLF5 is an early event in intestinal tumorigenesis in vivo. Collectively, these data indicate that intestinal tumor progression is associated with a change in the growth-related functions of KLF5 and that intestinal tumors down-regulate KLF5 expression by multiple mechanisms.

Received for publication, October 21, 2003 , and in revised form, January 13, 2004.

^* This work was supported by the Roswell Park Alliance Foundation, the Mae Stone Goode Foundation, National Institutes of Health Grants DK54909 and DK60632, and Roswell Park Cancer Center Core Grant CA16056. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article is dedicated to the late Dr. Alexander Bloch in recognition of his support and encouragement.

^|| To whom correspondence should be addressed: Dept. of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Tel.: 716-845-3090; Fax: 716-845-8857; E-mail: adrian.black{at}roswellpark.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Guo, K.-W. Zhao, X.-Y. Dong, X. Sun, and J.-T. Dong Acetylation of KLF5 Alters the Assembly of p15 Transcription Factors in Transforming Growth Factor-{beta}-mediated Induction in Epithelial Cells J. Biol. Chem., July 3, 2009; 284(27): 18184 - 18193. [Abstract] [Full Text] [PDF]

				T. Suzuki, D. Sawaki, K. Aizawa, Y. Munemasa, T. Matsumura, J. Ishida, and R. Nagai Kruppel-like Factor 5 Shows Proliferation-specific Roles in Vascular Remodeling, Direct Stimulation of Cell Growth, and Inhibition of Apoptosis J. Biol. Chem., April 3, 2009; 284(14): 9549 - 9557. [Abstract] [Full Text] [PDF]

				P. Guo, X.-Y. Dong, X. Zhang, K.-W. Zhao, X. Sun, Q. Li, and J.-T. Dong Pro-proliferative Factor KLF5 Becomes Anti-proliferative in Epithelial Homeostasis upon Signaling-mediated Modification J. Biol. Chem., March 6, 2009; 284(10): 6071 - 6078. [Abstract] [Full Text] [PDF]

				H. Wan, F. Luo, S. E. Wert, L. Zhang, Y. Xu, M. Ikegami, Y. Maeda, S. M. Bell, and J. A. Whitsett Kruppel-like factor 5 is required for perinatal lung morphogenesis and function Development, August 1, 2008; 135(15): 2563 - 2572. [Abstract] [Full Text] [PDF]

				Y. Yang, M.-P. Tetreault, Y. A. Yermolina, B. G. Goldstein, and J. P. Katz Kruppel-like Factor 5 Controls Keratinocyte Migration via the Integrin-linked Kinase J. Biol. Chem., July 4, 2008; 283(27): 18812 - 18820. [Abstract] [Full Text] [PDF]

				B. G. Goldstein, H.-H. Chao, Y. Yang, Y. A. Yermolina, J. W. Tobias, and J. P. Katz Overexpression of Kruppel-like factor 5 in esophageal epithelia in vivo leads to increased proliferation in basal but not suprabasal cells Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1784 - G1792. [Abstract] [Full Text] [PDF]

				J. X. Du, C. C. Yun, A. Bialkowska, and V. W. Yang Protein Inhibitor of Activated STAT1 Interacts with and Up-regulates Activities of the Pro-proliferative Transcription Factor Kruppel-like Factor 5 J. Biol. Chem., February 16, 2007; 282(7): 4782 - 4793. [Abstract] [Full Text] [PDF]

				Y. Yang, B. G. Goldstein, H. Nakagawa, and J. P. Katz Kruppel-like factor 5 activates MEK/ERK signaling via EGFR in primary squamous epithelial cells FASEB J, February 1, 2007; 21(2): 543 - 550. [Abstract] [Full Text] [PDF]

				C. Chen, A. K. Seth, and A. E. Aplin Genetic and Expression Aberrations of E3 Ubiquitin Ligases in Human Breast Cancer Mol. Cancer Res., October 1, 2006; 4(10): 695 - 707. [Abstract] [Full Text] [PDF]

				I. Sur, B. Rozell, V. Jaks, A. Bergstrom, and R. Toftgard Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis J. Cell Sci., September 1, 2006; 119(17): 3593 - 3601. [Abstract] [Full Text] [PDF]

				A. A. Hizli, A. R. Black, M. A. Pysz, and J. D. Black Protein Kinase C {alpha} Signaling Inhibits Cyclin D1 Translation in Intestinal Epithelial Cells J. Biol. Chem., May 26, 2006; 281(21): 14596 - 14603. [Abstract] [Full Text] [PDF]

				J. I. Fenton and N. G. Hord Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research Carcinogenesis, May 1, 2006; 27(5): 893 - 902. [Abstract] [Full Text] [PDF]

				D. Tong, K. Czerwenka, G. Heinze, M. Ryffel, E. Schuster, A. Witt, S. Leodolter, and R. Zeillinger Expression of KLF5 is a Prognostic Factor for Disease-Free Survival and Overall Survival in Patients with Breast Cancer Clin. Cancer Res., April 15, 2006; 12(8): 2442 - 2448. [Abstract] [Full Text] [PDF]

				C. Chen, X. Sun, P. Guo, X.-Y. Dong, P. Sethi, X. Cheng, J. Zhou, J. Ling, J. W. Simons, J. B. Lingrel, et al. Human Kruppel-like Factor 5 Is a Target of the E3 Ubiquitin Ligase WWP1 for Proteolysis in Epithelial Cells J. Biol. Chem., December 16, 2005; 280(50): 41553 - 41561. [Abstract] [Full Text] [PDF]