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Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1

Oncogene volume 28, pages 3702–3713 (2009)Cite this article

Abstract

The Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor promoting cell proliferation, cell-cycle progression and survival. A high expression level of KLF5 mRNA has been shown to be associated with shorter breast cancer patient survival. However, the mechanism of KLF5 action in breast cancer is still not clear. In this study, we found that both KLF5 and its downstream gene fibroblast growth factor binding protein 1 (FGF-BP) are co-expressed in breast cell lines and primary tumors. Manipulation of the KLF5 expression can positively regulate the FGF-BP mRNA and protein levels in multiple breast cell lines. In addition, the secreted FGF-BP protein in the conditional medium is also regulated by KLF5. Furthermore, we demonstrated that KLF5 binds and activates the FGF-BP promoter through a GC box by luciferase reporter, oligo pull down and chromatin immunoprecipitation (ChIP) assays. When FGF-BP is depleted by siRNA, KLF5 fails to promote cell proliferation in MCF10A, SW527 and TSU-Pr1. We further demonstrated that overexpression or addition of FGF-BP rescues the KLF5-knockdown-induced growth arrest in MCF10A cells. Finally, KLF5 significantly promotes MCF7 breast cancer cell xenograft growth in athymic nude mice. These findings suggest that KLF5 may promote breast cancer cell proliferation at least partially through directly activating the FGF-BP mRNA transcription. Understanding the mechanism of KLF5 action in breast cancer may result in useful diagnostic and therapeutic targets.

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Abbreviations

Ab:

antibody

ChIP:

chromatin immunoprecipitation

CM:

conditional media

ER:

estrogen receptor

FGF-BP:

fibroblast growth factor binding protein 1

IHC:

immunohistochemistry

KLF5:

Krüppel-like factor 5

RT–PCR:

reverse transcript–PCR

siRNA:

small interfering RNA

wt:

wild type

mt:

mutant

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Acknowledgements

This work was supported in part by a grant (BCTR0503705) from the Susan G Komen Breast Cancer Foundation, a grant from the American Cancer Society and a grant from the Department of Defense (W81XWH-07-1-0191). We thank Dr Chunhong Yan and Dr Jihe Zhao for providing the pRL-β-actin construct and the pBabe-puro retroviral system.

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Authors and Affiliations

  1. The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY, USA

    H -Q Zheng, Z Zhou, L Chaudhury & C Chen

  2. Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    J Huang

  3. Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    J -T Dong

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  1. H -Q Zheng
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Correspondence to C Chen.

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Zheng, HQ., Zhou, Z., Huang, J. et al. Krüppel-like factor 5 promotes breast cell proliferation partially through upregulating the transcription of fibroblast growth factor binding protein 1. Oncogene 28, 3702–3713 (2009). https://doi.org/10.1038/onc.2009.235

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