The First Affiliated Hospital, Department of Breast and Thyroid Surgery, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China.
Discov Med. 2024 Mar;36(182):559-570. doi: 10.24976/Discov.Med.202436182.52.
The epidermal growth factor receptor 2 () is overexpressed in 30% of breast cancers, and this overexpression is strongly correlated with a poor prognosis. Herceptin is a common treatment for HER2-positive breast cancer; however, cancer cells tend to adapt gradually to the drug, rendering it ineffective. The study revealed an association between the methylation status of the Homeobox C8 () gene and tumor development. Therefore, it is of paramount importance to delve into the interaction between and HER2-positive breast cancer, along with its molecular mechanisms. This exploration holds significant implications for a deeper understanding of the pathophysiological processes underlying HER2-positive breast cancer.
Tumor tissue and pathological data from patients with HER2-positive breast cancer were systematically collected. Additionally, the human HER2-positive breast cancer cell line, SKBR3, was cultured to assess both the expression level of and the degree of DNA methylation. The study aimed to explore the relationship between the relative expression of and the clinical characteristics of breast cancer patients. The expression level of and the promoter methylation of were verified by methylation treatment of SKBR3 breast cancer cells. The regulation of was meticulously carried out, leading to the division of the cells into distinct groups. The study further analyzed the expression levels and biological capabilities within each group. Finally, the and sensitivity of the cells to Herceptin, a common treatment for HER2-positive breast cancer, was measured to assess the efficacy of the drug.
In HER2-positive breast cancer cases characterized by poor methylation, there was an up-regulation of . Its expression was found to be correlated with key clinical factors such as tumor size, lymph node status, clinical tumor, node, metastasis (cTNM) staging, and Herceptin resistance ( < 0.05). Upon methylation of breast cancer cells, there was a significant decrease in expression ( < 0.05). The study revealed that overexpression of resulted in increased proliferation, cloning, and metastasis of HER2-positive breast cancer cells, along with a reduced apoptosis rate ( < 0.05). Conversely, interference with expression reversed this scenario ( < 0.05). A Herceptin-resistant substrain, POOL2, was established using SKBR3 cells. Animal studies demonstrated that overexpressing accelerated tumor development and enhanced POOL2 cells' resistance to Herceptin ( < 0.05). However, following interference with , POOL2 cells exhibited increased responsiveness to Herceptin, leading to a gradual reduction in tumor size ( < 0.05).
In HER2-positive breast cancer, the expression of is elevated in a manner dependent on DNA methylation, and this elevated expression is closely linked to the pathology of the patient. Interfering with expression demonstrates the potential to partially inhibit the development and spread of breast cancer, as well as to alleviate resistance to Herceptin.
表皮生长因子受体 2 () 在 30%的乳腺癌中过度表达，这种过度表达与预后不良密切相关。赫赛汀是治疗 HER2 阳性乳腺癌的常用药物；然而，癌细胞往往会逐渐适应药物，使其失效。研究揭示了同源盒 C8 () 基因的甲基化状态与肿瘤发展之间的关联。因此，深入研究与 HER2 阳性乳腺癌的相互作用及其分子机制至关重要。这一探索对于深入了解 HER2 阳性乳腺癌的病理生理过程具有重要意义。
系统收集 HER2 阳性乳腺癌患者的肿瘤组织和病理数据。此外，还培养了人 HER2 阳性乳腺癌细胞系 SKBR3，以评估 和 DNA 甲基化的表达水平。该研究旨在探讨 的相对表达与乳腺癌患者临床特征之间的关系。通过对 SKBR3 乳腺癌细胞进行甲基化处理，验证了 的表达水平和 的启动子甲基化。对 进行了细致的调控，将细胞分为不同的组。进一步分析了每组的表达水平和生物学功能。最后，测量了细胞对赫赛汀（一种治疗 HER2 阳性乳腺癌的常用药物）的 和 敏感性，以评估药物的疗效。
在 HER2 阳性乳腺癌中，低甲基化的病例中， 上调。其表达与肿瘤大小、淋巴结状态、临床肿瘤、淋巴结、转移 (cTNM) 分期和赫赛汀耐药有关 ( < 0.05)。乳腺癌细胞甲基化后， 表达明显下降 ( < 0.05)。研究表明， 过表达可促进 HER2 阳性乳腺癌细胞的增殖、克隆和转移，同时降低细胞凋亡率 ( < 0.05)。相反，干扰 表达则逆转了这一情况 ( < 0.05)。使用 SKBR3 细胞建立了赫赛汀耐药亚系 POOL2。动物研究表明，过表达 可加速肿瘤发展并增强 POOL2 细胞对赫赛汀的耐药性 ( < 0.05)。然而，干扰 后，POOL2 细胞对赫赛汀的敏感性增加，导致肿瘤体积逐渐缩小 ( < 0.05)。
在 HER2 阳性乳腺癌中， 的表达升高，且依赖于 DNA 甲基化，这种升高的表达与患者的病理密切相关。干扰 表达可能部分抑制乳腺癌的发展和扩散，并减轻赫赛汀的耐药性。
Zotero 插件