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

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-09-0329v1 204/3/223    most recent 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 Web of Science (1) Google Scholar Articles by Simmen, R C M Articles by Simmen, F A PubMed PubMed Citation Articles by Simmen, R C M Articles by Simmen, F A

¹ Department of Physiology and Biophysics
² Interdisciplinary Biomedical Sciences Program, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72202, USA
³ Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, Arkansas 72202, USA
⁴ Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA

(Correspondence should be addressed to R C M Simmen; Email: simmenrosalia{at}uams.edu)

Krüppel-like factors (KLFs), of which there are currently 17 known protein members, belong to the specificity protein (Sp) family of transcription factors and are characterized by the presence of Cys₂/His₂ zinc finger motifs in their carboxy-terminal domains that confer preferential binding to GC/GT-rich sequences in gene promoter and enhancer regions. While previously regarded to simply function as silencers of Sp1 transactivity, many KLFs are now shown to be relevant to human cancers by their newly identified abilities to mediate crosstalk with signaling pathways involved in the control of cell proliferation, apoptosis, migration, and differentiation. Several KLFs act as tumor suppressors and/or oncogenes under distinct cellular contexts, underscoring their prognostic potential for cancer survival and outcome. Recent studies suggest that a number of KLFs can influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Since inappropriate sensitivity or resistance to steroid hormone actions underlies endocrine-related malignancies, we consider the intriguing possibility that dysregulation of expression and/or activity of KLF members is linked to the pathogenesis of endometrial and breast cancers. In this review, we focus on recently described mechanisms of actions of several KLFs (KLF4, KLF5, KLF6, and KLF9) in cancers of the mammary gland and uterus. We suggest that understanding the mode of actions of KLFs and their functional networks may lead to the development of novel therapeutics to improve current prospects for cancer prevention and cure.

This article has been cited by other articles:

				J. M. P. Pabona, Z. Zeng, F. A. Simmen, and R. C. M. Simmen Functional Differentiation of Uterine Stromal Cells Involves Cross-Regulation between Bone Morphogenetic Protein 2 and Kruppel-Like Factor (KLF) Family Members KLF9 and KLF13 Endocrinology, July 1, 2010; 151(7): 3396 - 3406. [Abstract] [Full Text] [PDF]

				P. Kannan-Thulasiraman, D. D. Seachrist, G. H. Mahabeleshwar, M. K. Jain, and N. Noy Fatty Acid-binding Protein 5 and PPAR{beta}/{delta} Are Critical Mediators of Epidermal Growth Factor Receptor-induced Carcinoma Cell Growth J. Biol. Chem., June 18, 2010; 285(25): 19106 - 19115. [Abstract] [Full Text] [PDF]

				C. D. Simmons, J. M. P. Pabona, Z. Zeng, M. C. Velarde, D. Gaddy, F. A. Simmen, and R. C. M. Simmen Response of adult mouse uterus to early disruption of estrogen receptor-{alpha} signaling is influenced by Kruppel-like factor 9 J. Endocrinol., May 1, 2010; 205(2): 147 - 157. [Abstract] [Full Text] [PDF]