Department of Biology, College of Science, Yonsei University, Seoul, 120-749, Korea.
Mol Cells. 2010 Feb 28;29(2):217-21. doi: 10.1007/s10059-010-0052-9. Epub 2010 Jan 28.
To escape the immune system, tumor cells may remove surface molecules such as the major histocompatibility complex (MHC) and co-stimulatory molecules, which are essential for recognition by lymphocytes. Down-regulation of the co-stimulatory molecules CD70 (TNFSF7) and CD80 may contribute to tumor cell survival; however, the mechanism of down-regulation of the TNFSF7 gene during tumorigenesis is poorly understood. Here we present evidence indicating that TNFSF7 gene expression is epigenetically down-regulated via DNA hypermethylation within its promoter region during progression in breast cancer cells in the isogenic MCF10 model. Bisulfite sequencing revealed that the CpG pairs at the proximal region of the TNFSF7 promoter are heavily methylated during progression of breast cancer cells but that methylation of the more distal sequences was not changed considerably. Thus, this epigenetic silencing of the TNFSF7 gene via hypermethylation of its proximal region may allow the benign and invasive MCF10 variants to escape immune surveillance.
为了逃避免疫系统，肿瘤细胞可能会去除表面分子，如主要组织相容性复合体 (MHC) 和共刺激分子，这些分子对于淋巴细胞的识别至关重要。共刺激分子 CD70 (TNFSF7) 和 CD80 的下调可能有助于肿瘤细胞的存活；然而，肿瘤发生过程中 TNFSF7 基因下调的机制还不清楚。在这里，我们提供的证据表明，在 MCF10 同基因模型中乳腺癌细胞的进展过程中，TNFSF7 基因通过其启动子区域内的 DNA 超甲基化而被表观遗传地下调。亚硫酸氢盐测序显示，在乳腺癌细胞的进展过程中，TNFSF7 启动子近端的 CpG 对高度甲基化，但更远端序列的甲基化变化不大。因此，这种通过其近端区域的高度甲基化导致的 TNFSF7 基因的表观遗传沉默可能使良性和侵袭性 MCF10 变体逃避免疫监视。
