Radhi Janan Husain, El-Hagrasy Ahmed Mohsen Abbas, Almosawi Sayed Husain, Alhashel Abdullatif, Butler Alexandra E
School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain (RCSI Bahrain), Building No. 2441, Road 2835, Busaiteen P.O. Box 15503, Bahrain.
Research Department, Royal College of Surgeons in Ireland-Medical University of Bahrain (RCSI Bahrain), Building No. 2441, Road 2835, Busaiteen P.O. Box 15503, Bahrain.
Cancers (Basel). 2025 Jan 21;17(3):337. doi: 10.3390/cancers17030337.
Osteoprotegerin (OPG), encoded by the gene, 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.
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.
Studies have demonstrated that certain SNPs in the OPG gene, specifically and , 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.
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.
骨保护素（OPG）由该基因编码，通过多种途径与乳腺癌的发生发展相关，包括与核因子κB受体激活剂（RANK）配体相互作用、与TRAIL等诱导凋亡蛋白相互作用以及单核苷酸多态性（SNP）等基因变异，直接改变基因表达。本综述旨在研究OPG表达在乳腺癌中的作用。
使用PubMed Medline、谷歌学术和ScienceDirect进行全面的文献检索。仅纳入从创刊到2024年9月的全文英文出版物。
研究表明，OPG基因中的某些SNP，特别是[具体SNP名称1]和[具体SNP名称2]，与乳腺癌发生风险较高相关。此外，OPG作为TRAIL诱饵受体的功能可能抑制癌细胞死亡。此外，正在研究血清中的OPG及其与BRCA突变的相互作用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细胞增殖、血管生成和非整倍体来促进肿瘤发生。此外，OPG介导白细胞介素-1β的促肿瘤作用，并且通过其在失调的RANK信号传导中的作用，可能作为乳腺癌风险的生物标志物，特别是在BRCA1突变携带者中。最后，已发现在小鼠模型中使用重组OPG具有抗肿瘤作用。
在本综述中，研究了OPG在乳腺癌中的作用。OPG在乳腺癌肿瘤发生中具有多方面作用，并通过基因变异（SNP）、与肿瘤坏死因子相关凋亡诱导配体（TRAIL）相互作用以及调节血管生成、细胞存活和转移的促肿瘤微环境效应发挥作用。此外，OPG作为肿瘤抑制因子和促进因子的双重作用可能成为增强细胞凋亡、限制骨转移和调节肿瘤微环境的治疗靶点。虽然目前已知很多，但仍需要进一步研究以全面阐明OPG的作用。
