The Kru¨ppel-like factor 5 (KLF5) is a zinc-finger transcription factor promoting cell proliferation, cellcycle 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.
Background:The mechanism by which the KLF5 transcription factor promotes breast cancer is not entirely understood. Results: KLF5 promotes breast cell proliferation partially through inducing mPGES1 gene expression. Conclusion: mPGES1 is a direct transcriptional target gene of KLF5. Significance: We discovered a new functional mechanism for KLF5 and a regulation mechanism for mPGES1.
The antidiarrhoeal activity of the seed extract of Albizzia lebbeck (Benth.) was investigated employing conventional rodent models of diarrhoea, i.e. castor oil-induced diarrhoea, upper gastrointestinal transit (u.g.t.) and fluid secretion. It was found that the aqueous methanol extract of Albizzia lebbeck seeds (2.5-5 mg/kg i.p.) possessed antidiarrhoeal activity which strengthens the earlier use of the seeds in the treatment of diarrhoea and dysentery. The antidiarrhoeal dose of the extract was at least 10-30 times less than the LD(50) dose. The extract (2.5-5 mg/kg i.p.) potentiated the antidiarrhoeal activity of loperamide (1 mg/kg i.p.). Nalaxone (0.5 mg/kg i.p.) significantly inhibited the antidiarrhoeal activity of the extract as well as loperamide, thus indicating a role of the opioid system in the antidiarrhoeal activity of the extract.
Glutamine aminohydrolase is found to be present in microsomal and soluble supernatant in liver of EAC-bearing mice. Enzymes obtained from these two sources were characterized and found to behave differently from the mitochondrial glutaminase of both normal and tumour-bearing mice.
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