Introduction: Osteoprotegerin (OPG), encoded by theTNFRSF11Bgene, is linked to the development of breast cancer via several pathways, including interactions with the receptor activator of nuclear factor-κB (RANK) ligands, apoptosis-inducing proteins like TRAIL, and genetic variations such as single nucleotide polymorphisms (SNPs), directly altering gene expression. This review aims to investigate the role of OPG expression in breast cancer. Methods: A comprehensive literature search was conducted using PubMed Medline, Google Scholar, and ScienceDirect. Only full-text English publications from inception to September 2024 were included. Results: Studies have demonstrated that certain SNPs in the OPG gene, specificallyrs3102735andrs2073618, are linked to a higher risk of breast cancer development. Additionally, OPG’s function as a TRAIL decoy receptor may inhibit the death of cancer cells. Furthermore, OPG in the serum and its interactions with BRCA mutations are being investigated for their potential influence on breast cancer progression. Studies have found that OPG promotes tumorigenesis by enhancing cell proliferation, angiogenesis, and aneuploidy in normal mammary epithelial cells. Moreover, OPG mediates the tumor-promoting effects of interleukin-1 beta and may serve as a biomarker for breast cancer risk, particularly in BRCA1 mutation carriers, through its role in dysregulated RANK signaling. Lastly, the use of recombinant OPG in mouse models has been found to exert anti-tumor effects. Conclusions: In this review, the role of OPG in breast cancer is examined. OPG has a multifaceted role in breast cancer tumorigenesis and exerts its effects through genetic variations (SNPs), interactions with TNF-related apoptosis-inducing ligand (TRAIL), and the modulation of the pro-tumorigenic microenvironment effects of angiogenesis, cell survival, and metastasis. Additionally, OPG’s dual role as a tumor suppressor and promoter serves as a possible therapeutic target to enhance apoptosis, limit bone metastasis, and modulate the tumor microenvironment. Whilst much is now known, further studies are necessary to fully delineate the role of OPG.
引言：骨保护素（OPG）由TNFRSF11B基因编码，通过多种途径与乳腺癌的发生发展相关，包括与核因子κB受体活化因子（RANK）配体的相互作用、与TRAIL等凋亡诱导蛋白的关联，以及单核苷酸多态性（SNPs）等直接改变基因表达的遗传变异。本综述旨在探讨OPG表达在乳腺癌中的作用。方法：通过PubMed Medline、Google Scholar和ScienceDirect数据库进行系统性文献检索，仅纳入自建库至2024年9月的英文全文文献。结果：研究表明，OPG基因中的特定SNPs（尤其是rs3102735和rs2073618）与乳腺癌发病风险升高相关。此外，OPG作为TRAIL诱饵受体的功能可能抑制癌细胞死亡。血清OPG水平及其与BRCA基因突变的相互作用正被探索其对乳腺癌进展的潜在影响。研究发现，OPG通过增强正常乳腺上皮细胞的增殖、血管生成和非整倍性促进肿瘤发生。同时，OPG介导白细胞介素-1β的促肿瘤效应，并可能通过参与RANK信号通路失调，成为乳腺癌（尤其是BRCA1突变携带者）的风险生物标志物。最后，小鼠模型中使用重组OPG显示出抗肿瘤效应。结论：本综述系统阐述了OPG在乳腺癌中的作用机制。OPG通过遗传变异（SNPs）、与肿瘤坏死因子相关凋亡诱导配体（TRAIL）的相互作用，以及调控血管生成、细胞存活和转移等促肿瘤微环境效应，在乳腺癌发生发展中发挥多面性作用。其兼具抑癌与促癌的双重特性，可能成为增强细胞凋亡、抑制骨转移及调控肿瘤微环境的潜在治疗靶点。尽管已有较多研究，仍需进一步深入探索以全面阐明OPG的作用机制。
肿瘤(癌症)患者之家