Abstract：
Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERβ signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.
摘要：
内分泌治疗,尤其是他莫昔芬,雌激素受体阳性（ER阳性）乳腺癌患者的预后显着改善。然而,这种治疗的临床效用往往受到内分泌抵抗发展的阻碍。因此,全面了解ER阳性乳腺癌癌变和内分泌耐药的潜在机制对于克服这一临床挑战至关重要.在这项研究中,我们研究了MICAL-L2在ER阳性乳腺癌中的表达及其对患者预后的影响.我们观察到在ER阳性乳腺癌中MICAL-L2表达的显著上调，这与这些患者预后较差有关。此外，我们发现雌激素-ERβ信号促进MICAL-L2的表达。功能上,我们的研究表明,MICAL-L2不仅在ER阳性乳腺癌的肿瘤发生中起致癌作用,而且还影响ER阳性乳腺癌细胞对他莫昔芬的敏感性.机械上,作为雌激素反应基因，MICAL-L2促进ER阳性乳腺癌细胞中Akt/mTOR信号通路的激活。总的来说，我们的研究结果表明,MICAL-L2可作为ER阳性乳腺癌的潜在预后标志物,并且是改善内分泌治疗和开发该亚型乳腺癌治疗方法的有前景的分子靶标.
