Department of Pathology.
Laboratory of Clinical and Experimental Pathology.
J Histochem Cytochem. 2018 Oct;66(10):709-721. doi: 10.1369/0022155418797315. Epub 2018 Aug 22.
The role of Runt-related transcription factor 3 ( RUNX3) gene in breast cancer remains not fully understood. We studied the correlation between RUNX3 gene promoter methylation and estrogen receptor (ER) expression status in breast cancer. Three breast cancer cell lines and 113 formalin-fixed, paraffin-embedded breast cancer tissue samples were analyzed for RUNX3 expression. Methylation-specific polymerase chain reaction was used to analyze RUNX3 methylation on the samples. Migration and invasion ability were evaluated in MCF7 cell line (RUNX3 methylated) treated with methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) to study the effect of RUNX3 methylation status. Our data showed that the expression of RUNX3 was high in MCF10A but not in MCF7 and SKBR3 cell lines, while the RUNX3 promoter showed hypermethylation in MCF7 but not in MCF10A and SKBR3. In tissues samples, Immunohistochemical (IHC) expression of RUNX3 protein was higher in ER-negative samples than in ER-positive cases, and it was negatively correlated with the methylation status of the RUNX3 gene promoter. Proliferation, migration, and invasion of MCF7 were suppressed when 5-Aza-CdR treated. Also, the hypermethylation status of RUNX3 gene promoter was reversed and RUNX3 expression was increased. In summary, our data suggest that hypermethylation of the RUNX3 gene promoter may play an important role in ER-positive breast tumor progression.
Runt 相关转录因子 3（RUNX3）基因在乳腺癌中的作用尚不完全清楚。我们研究了 RUNX3 基因启动子甲基化与乳腺癌中雌激素受体（ER）表达状态的相关性。分析了三种乳腺癌细胞系和 113 例福尔马林固定、石蜡包埋的乳腺癌组织样本中的 RUNX3 表达。使用甲基化特异性聚合酶链反应分析了样本中的 RUNX3 甲基化。在 MCF7 细胞系（RUNX3 甲基化）中用甲基化抑制剂 5-氮杂-2'-脱氧胞苷（5-Aza-CdR）处理，评估迁移和侵袭能力，以研究 RUNX3 甲基化状态的影响。我们的数据表明，MCF10A 中的 RUNX3 表达较高，但 MCF7 和 SKBR3 细胞系中没有表达，而 MCF7 中的 RUNX3 启动子表现出高度甲基化，但 MCF10A 和 SKBR3 中没有。在组织样本中，RUNX3 蛋白的免疫组化（IHC）表达在 ER 阴性样本中高于 ER 阳性病例，并且与 RUNX3 基因启动子的甲基化状态呈负相关。用 5-Aza-CdR 处理后，MCF7 的增殖、迁移和侵袭受到抑制。此外，RUNX3 基因启动子的高度甲基化状态被逆转，RUNX3 表达增加。总之，我们的数据表明，RUNX3 基因启动子的高度甲基化可能在 ER 阳性乳腺癌的进展中起重要作用。
