Journal Article

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

Zhou, Z, Huang, J, Zheng, H -Q, Chen, C, Chaudhury, L, Dong, J -T

2009

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Apoptosis / Base Sequence / Binding Sites / Biological and medical sciences / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cell Biology / Cell cycle / Cell growth / Cell Line, Tumor / Cell physiology / Cell Proliferation / Cell survival / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Chromatin / Female / Fibroblast growth factors / Fibroblasts / Fundamental and applied biological sciences. Psychology / GC Rich Sequence / Gene expression / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Genes / Genetic aspects / Genetics / Growth factors / Gynecology. Andrology. Obstetrics / Human Genetics / Humans / Immunohistochemistry / Immunoprecipitation / Intercellular Signaling Peptides and Proteins / Internal Medicine / Kruppel-Like Transcription Factors - deficiency / Kruppel-Like Transcription Factors - genetics / Kruppel-Like Transcription Factors - metabolism / Mammary gland diseases / Medical sciences / Medicine / Medicine & Public Health / Mice / Molecular and cellular biology / Molecular genetics / Oncology / original-article / Physiological aspects / Promoter Regions, Genetic - genetics / Protein binding / Proteins / Risk factors / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA, Small Interfering - genetics / Rodents / siRNA / Therapeutic targets / Transcription, Genetic / Transcription. Transcription factor. Splicing. Rna processing / Tumors / Up-Regulation / Xenografts / Zinc finger proteins