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Klotho inhibits the capacity of cell migration and invasion in cervical cancer
CHANG, BOOGI,KIM, JINSUN,JEONG, DONGJUN,JEONG, YUJUN,JEON, SEOB,JUNG, SAM-IL,YANG, YOUNG,KIM, KEUN IL,LIM, JONG-SEOK,KIM, CHANGJIN,LEE, MYEONG-SOK Spandidos Publications 2012 ONCOLOGY REPORTS Vol.28 No.3
<P>Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers. However, the mechanisms of Wnt activation in cervical cancer remain largely unknown. In the present study, we demonstrate that Klotho, a Wnt antagonist, is downregulated in invasive human cervical tumors and in a cell line we analyzed. Our data demonstrated that in?vivo Klotho expression was not observed in invasive cervical carcinoma. In?vitro restoration of Klotho expression in SiHa cells resulted in a decreased cell motility and invasiveness through upregulation of E-cadherin, downregulation of N-cadherin and reduced expression of MMP7 and -9. Ectopic expression of Klotho also reduced the expression of the epithelial-to-mesenchymal transition (EMT) transcription factors Slug and Twist. Furthermore, Klotho causes a significant inhibition of the Wnt/β-catenin pathway in cervical cancer cells, as supported by the expression of Wnt/β-catenin transcriptional target genes such as c-Myc and cyclin?D1. Consequently, our findings demonstrate for the first time that Klotho regulates tumor invasion through the EMT process and provide novel mechanistic insights into the role of Klotho in cervical cancer progression and contribute to treatment for metastatic cervical cancer patients.</P>
The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer
Jung, Samil,Jeong, Dongjun,Kim, Jinsun,Yi, Lisha,Koo, Keunhoe,Lee, Jaehyouk,Lee, Soon-Duck,Park, Jin-Wha,Chang, Boogi,Kim, Chang-Hwan,Kim, Chang-Jin,Lee, Myeong-Sok Spandidos Publications 2010 ONCOLOGY REPORTS Vol.23 No.6
<P>The homo sapiens LIM homeobox domain LHX6 gene, hLHX6, is a putative transcription regulator with homeo-domain. Multiple cytosine guanine dinucleotides (CpG island) are found in the genomic sequences between exon 4a and exon 5 of the gene encoding hLHX6s (alternative short iso-form of hLHX6 gene). This specific CpG island, hLHX6-HMR, is found frequently hypermethylated in 7 cervical cancer cell lines as shown in MSP, BSP, and COBRA assays. Methylation densities were also investigated with human tissue samples with a distinctive degree of malignant transformation. Our data showed that the hLHX6-HMR was rarely or partly methylated in the normal and CIN I cells, respectively. In contrast, it was frequently hypermethylated in CIN II, CIN III, and invasive carcinoma cells. In summary, this methylation study led to two conclusions. First, hLHX6-HMR hypermethylation is exclusively associated with cervical carcinogenesis. Second, the epigenetic change in hLHX6-HMR seems to start at CIN I, relatively early stage of cervical cancer development. Therefore, hLHX6-HMR can be used as an effective and sensitive methylation biomarker for early diagnosis of cervical cancer.</P>