Synergistic Action between Aberrant Expression of DNA Methyltransferase 1 and Folate Deficiency in t

来源 :BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会) | 被引量 : 0次 | 上传用户:qiwa99
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  DNMT methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation status.Aberrant DNA methylation is a recognized feature of human cancers, and folate is directly involved in DNA methylation via onecarbon metabolism.Previous reports also suggest that folate deficiency is associated with increased risk of many cancers.A cross-sectional study was conducted to test the hypothesis that folate status and aberrant expression of DNMT1 show a progressive change across stages of cervical pathology from normal cells to cervical cancer.The expression of DNMT1 protein and mRNA, and levels of serum folate were detected in 238 women with a diagnosis of normal cervix (n =53), cervical intraepithelial neoplasm (CIN*, n =52;CIN*/*, n =53), or cervix squamous cell carcinoma (SCC;n =80).Additionally, the expression of DNMT1 protein and mRNA was measured in cervical cancer cells (Caski and C33A) treated by different concentration of folate.The serum folate levels were descended, the expression of DNMT1 protein and mRNA was increased gradually with the severity of the cervix lesions (P<0.001).It was found that folate supplement was able to reduce the proliferation of Caski and C33A cells (r=0.978,P=0.002;r=0.984,P<0.001) and the expression of DNMT1 protein (r=-0.859, P=0.01;r=-0.914,P<0.001) or mRNA (r=-0.297,P=0.159;r=0.433,P=0.034).Our finding indicated that there might be a synergistic action between low-level of folate and aberrant expression of DNMT1 in the progression of cervix carcinogenesis.Sufficient foleta is able to effectively inhibit the growth of cervical cancer cells and counteract transcriptional and posttranscriptional aberration of DNMT1.
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