乳腺癌 (BC) 主要发生在女性身上，每年导致无数死亡。有效治疗靶点的确定将有助于BC患者，并增加寻找治愈方法的可能性。相似序列家族84成员B (FAM84B) 已被卷入多种癌症的发展，但其在BC中的功能尚待探索。本研究通过在线数据库分析发现，FAM84B在BC患者组织中的表达较高，特别是在乳腺内上皮BC组织中，而在相应的正常组织中表达较低；此外，增加的FAM84B表达与预后不良有关。此外，蛋白质印迹分析表明，与正常和基底细胞样BC细胞系相比，FAM84B在乳腺内上皮BC细胞系中高度表达。此外，还采集了临床BC患者组织并进行了蛋白质印迹和免疫组化分析，结果显示FAM84B主要在乳腺内上皮BC样本中表达。因此，为了确定FAM84B在乳腺内上皮BC细胞中的功能，制备了具有FAM84B缺失和过表达的乳腺内上皮BC细胞系。此外，利用体外（细胞增殖、创伤愈合、集落形成和入侵试验）和体内（皮下异种移植实验）评估了FAM84B的功能，结果显示FAM84B调节细胞增殖而不影响细胞侵袭。此外，在ZR-75-1 FAM84B缺失和过表达细胞中的RNA测序分析结果显示，FAM84B可能影响TNF信号通路。随后，死亡受体信号通路的蛋白质印迹分析和NF-κB p65定位的免疫荧光分析揭示出FAM84B影响了死亡受体信号通路并促进了NF-κB p65核入。总结，我们发现FAM84B通过激活NF-κB和死亡受体信号通路促进乳腺内上皮BC的肿瘤发生。Copyright © 2023. Elsevier GmbH 发表。

Breast cancer (BC) occurs predominantly in women and leads to numerous deaths every year. The identification of effective therapeutic targets will benefit BC patients and increase the likelihood of finding a cure. Family with similar sequence 84, member B (FAM84B) has been implicated in the progression of many kinds of cancers, but its function in BC remains to be explored. In this study, online database analysis revealed that FAM84B expression was higher in BC patient tissues, especially in luminal BC tissues, than in the corresponding normal tissues; furthermore, increased FAM84B expression was related to poor prognosis. Additionally, western blot (WB) analysis revealed that the FAM84B protein was highly expressed in luminal BC cell lines compared to normal and basal-like BC cell lines. Moreover, clinical BC patient tissues were collected and subjected to WB and immunohistochemical (IHC) analyses, and the results showed that FAM84B was expressed mainly in luminal BC samples. Therefore, to determine the function of FAM84B in luminal BC cells, luminal BC cell lines with FAM84B knockout and overexpression were generated. In addition, the functions of FAM84B were evaluated in vitro (via cell proliferation, wound healing, colony formation and invasion assays) and in vivo (via a subcutaneous xenograft experiment), and the results showed that FAM84B regulated cell proliferation but not cell invasion. Furthermore, the results of RNA sequencing analysis in ZR-75-1 FAM84B knockout and FAM84B-overexpressing cells showed that FAM84B could affect the TNF signaling pathway. Subsequently, WB analysis of death receptor signaling and immunofluorescence (IF) analysis of NF-κB p65 localization revealed that FAM84B affected death receptor signaling and promoted NF-κB p65 nuclear entry. In conclusion, we found that FAM84B promotes luminal BC tumorigenesis through the activation of the NF-κB and death receptor signaling pathways.Copyright © 2023. Published by Elsevier GmbH.