Dynamic Down-Regulation Of Kruppel-Like Factor 4 (Klf4) In Colorectal Adenoma-Carcinoma Sequence

MOLECULAR CANCER THERAPEUTICS(2007)

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摘要
C278 Kruppel-like factors 4(KLF4)is crucial for maintaining homeostasis and terminally differentiated epithelial cells of the gastrointestinal tract. The role of KLF4 in colorectal cancer is emerging. However, previous studies only investigated KLF4 expression in a limited number of colorectal cancers and lacked specific clinicopathological analysis. In this study, we made a large clinicopathlogical survey on KLF4 expression in colorectal adenoma and cancer. Aims: To explore the role and significance of KLF4 expression in colorectal cancer initiation and progression. Methods and Results: We used Real-time PCR and immunostaining to detect KLF4 expression in colorectal adenoma and cancer. The large clinicopathlogical survey confirmed a sequential downregulation of KLF4 in the whole sequence of normal mucosa, adenoma and cancer (p In vitro study found elevated KLF4 mRNA expression in SW620 and RKO cells with 5-aza-dC or butyrate sodium treatment, implicating the underlying aberrant epigenetic modifications in regulating KLF4 expression in colorectal cancer. Conclusions: KLF4 is associated with terminal differentiation in colorectal epithelium and drastically downregulated in colorectal adenomas and cancers via possible epigenetic modifications. Loss of KLF4 protein expression might contribute to assessing prognosis in colorectal cancer with lymph node metastasis.
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klf4,factor,down-regulation,ppel-like,adenoma-carcinoma
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