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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Expression of RUNX3 gene, methylation status and clinicopathological significance in breast cancer and breast cancer cell lines.
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Expression of RUNX3 gene, methylation status and clinicopathological significance in breast cancer and breast cancer cell lines.

机译：RUNX3基因在乳腺癌和乳腺癌细胞系中的表达，甲基化状态及临床病理意义。

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BACKGROUND: Runt-related transcription factor 3 (RUNX3) is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. In this study, we aimed to analyze the methylation status of the RUNX3 promoter in breast cancer and to evaluate the relationship between RUNX3 expression and breast carcinogenesis and prognosis. METHODS: RT-PCR and Western blot were applied on 5 breast cancer cell lines, the human normal breast cell line Hs578Bst and 30 pairs of breast cancer and their matching normal breast tissues to detect mRNA and protein expression of the RUNX3 gene. Methylation-specific PCR was employed to detect the methylation status of the RUNX3 promoter. Immunohistochemical study was performed to analyze RUNX3 protein expression in 88 breast cancer tissues and 40 breast fibroadenomas. RESULTS: The expression of RUNX3 mRNA and protein were negative in 3 breast cancer cell lines (T47D, MCF7 and SKBR3) as analyzed by RT-PCR and Western blotting. Hypermethylation of the RUNX3 promotor was identified in the T47D and MCF7 cell lines, but was not detected in SKBR3. Western blot analysis showed that the RUNX3 protein of 44 kDa was detected in 15 of 30 (50%) breast cancers. However, RUNX3 protein was detected in all normal breast tissues. Methylation was detected in 13 of the 15 tissues (86.67%) that did not express RUNX3 protein, but was never detected in any surrounding normal tissues. Immunohistochemistry results revealed that the positive rate of RUNX3 protein expression in breast cancer (35.23%) was much lower than that in breast fibroadenoma (85%). RUNX3 expression was correlated with tumor infiltration, clinical stage, lymph node metastasis and the expression of estrogen and progesterone receptor (p < 0.05), but was not related to age, tumor types and pathological grade (p > 0.05). The survival rate of the patients with RUNX3-positive expression was higher than that with RUNX3-negative expression (p < 0.05). CONCLUSIONS: The expression of RUNX3 gene is decreased in breast cancer. The RUNX3 gene may play an important role in the carcinogenesis of breast cancer. The mechanism of its inactivation may be hypermethylation of the promoter. With the increased progression of breast cancer, the expression of RUNX3 protein tends to decrease. The expression of RUNX3 protein has a definite value in judging prognosis in breast cancer.
机译：背景：矮子相关转录因子3（RUNX3）是一种新型的抑癌基因，在胃癌中经常被启动子的高甲基化沉默。在这项研究中，我们旨在分析RUNX3启动子在乳腺癌中的甲基化状态，并评估RUNX3表达与乳腺癌癌变和预后之间的关系。方法：对5个乳腺癌细胞株，人正常乳腺癌细胞株Hs578Bst和30对乳腺癌及其匹配的正常乳腺癌组织进行RT-PCR和Western blot检测RUNX3基因的mRNA和蛋白表达。甲基化特异性PCR用于检测RUNX3启动子的甲基化状态。进行了免疫组织化学研究，以分析RUNX3蛋白在88个乳腺癌组织和40个乳腺癌纤维腺瘤中的表达。结果：通过RT-PCR和Western blotting分析，RUNX3 mRNA和蛋白在3种乳腺癌细胞（T47D，MCF7和SKBR3）中均为阴性。在T47D和MCF7细胞系中鉴定出RUNX3启动子的超甲基化，但在SKBR3中未检测到。蛋白质印迹分析表明，在30个乳腺癌中，有15个（50％）检测到44 kDa的RUNX3蛋白。但是，在所有正常乳腺组织中均检测到RUNX3蛋白。在15个未表达RUNX3蛋白的组织中，有13个（占86.67％）检测到甲基化，但在周围的正常组织中从未检测到甲基化。免疫组织化学结果显示，乳腺癌中RUNX3蛋白表达的阳性率（35.23％）远低于乳腺纤维腺瘤（85％）。 RUNX3的表达与肿瘤的浸润，临床分期，淋巴结转移以及雌激素和孕激素受体的表达有关（p <0.05），但与年龄，肿瘤类型和病理分级无关（p> 0.05）。 RUNX3阳性表达患者的生存率高于RUNX3阴性表达的患者（p <0.05）。结论：乳腺癌中RUNX3基因的表达降低。 RUNX3基因可能在乳腺癌的癌变过程中起重要作用。其失活的机制可能是启动子的高甲基化。随着乳腺癌进展的增加，RUNX3蛋白的表达趋于降低。 RUNX3蛋白的表达在判断乳腺癌预后中具有一定的价值。

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