期刊
EXPERIMENTAL CELL RESEARCH
卷 413, 期 1, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2022.113062
关键词
Bisulfite sequencing PCR (BSP); Breast cancer; CpG; DNA Methylation
This study found that increased transcription of CYP1A1 in breast cancer is correlated with hypermethylation of a specific CpG block and upregulation of antiapoptotic protein BCL-2. The hypermethylation of this CpG block may serve as a potential biomarker for diagnosis and progression of breast cancer.
Having broad specificity for xenobiotics metabolism throughout the body, cytochrome P450 (CYP) isoform 1A1 is of key relevance for carcinogenesis. However, the oncogenic potential of its altered transcription and the underlying mechanism has not been well-established in breast cancer. Direct bisulfite sequencing PCR (BSP) of the CYP1A1 promoter, enriched by 113 CpGs within and flanking the xenobiotic response elements (XREs) 2 to 10, in paired cancerous and normal tissues from 40 breast cancer patients revealed three distinctly methylated patterns; unmethylated (XREs 2 to 6) and completely methylated (XREs 7 and 8) CpGs, in common for the normal and cancerous tissues, and a putative 171bp CpG block (XREs 9 and 10) contiguously hypermethylated in the tumor tissues. Increased transcription of CYP1A1, observed for the cancerous tissues, was correlated with the hypermethylation of given CpG block, besides simultaneously being associated with upregulation of the antiapoptotic BCL-2. Clinical value of the methylation changes, investigated based on the comparisons between the tissue cohorts of different clinicopathological features, exhibited gradual hypermethylation of the corresponding CpG block following disease progression as well as lymphatic involvement. Hypermethylation of given CpG block may has potential to be used as a biomarker for diagnosis and progression of breast cancer.
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