Abstract：
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. FAM3B, a secreted protein, has been extensively studied in various types of tumors. However, its function in breast cancer remains poorly understood.
METHODS: We analyzed FAM3B expression data from breast cancer patients available at TCGA database and overall survival was analyzed by using the Kaplan-Meier plotter. MDA-MB-231 TNBC tumor cell line and hormone-responsive MCF-7 cell lines were transfected to overexpress FAM3B. We assessed cell death, tumorigenicity, and invasiveness in vitro through MTT analysis, flow cytometry assays, anchorage-independent tumor growth, and wound healing assays, respectively. We performed in vivo evaluation by tumor xenograft in nude mice.
RESULTS: In silico analysis revealed that FAM3B expression was lower in all breast tumors. However, TNBC patients with high FAM3B expression had a poor prognosis. FAM3B overexpression protected MDA-MB-231 cells from cell death, with increased expression of Bcl-2 and Bcl-xL, and reduced caspase-3 activity. MDA-MB-231 cells overexpressing FAM3B also exhibited increased tumorigenicity and migration rates in vitro, displaying increased tumor growth and reduced survival rates in xenotransplanted nude mice. This phenotype is accompanied by the upregulation of EMT-related genes Slug, Snail, TGFBR2, vimentin, N-cadherin, MMP-2, MMP-9, and MMP-14. However, these effects were not observed in the MCF-7 cells overexpressing FAM3B.
CONCLUSIONS: FAM3B overexpression contributes to tumor growth, promotion of metastasis, and, consequently, leads to a poor prognosis in the most aggressive forms of breast cancer. Future clinical research is necessary to validate FAM3B as both a diagnostic and a therapeutic strategy for TNBC.
METHODS: We analyzed FAM3B expression data from breast cancer patients available at TCGA database and overall survival was analyzed by using the Kaplan-Meier plotter. MDA-MB-231 TNBC tumor cell line and hormone-responsive MCF-7 cell lines were transfected to overexpress FAM3B. We assessed cell death, tumorigenicity, and invasiveness in vitro through MTT analysis, flow cytometry assays, anchorage-independent tumor growth, and wound healing assays, respectively. We performed in vivo evaluation by tumor xenograft in nude mice.
RESULTS: In silico analysis revealed that FAM3B expression was lower in all breast tumors. However, TNBC patients with high FAM3B expression had a poor prognosis. FAM3B overexpression protected MDA-MB-231 cells from cell death, with increased expression of Bcl-2 and Bcl-xL, and reduced caspase-3 activity. MDA-MB-231 cells overexpressing FAM3B also exhibited increased tumorigenicity and migration rates in vitro, displaying increased tumor growth and reduced survival rates in xenotransplanted nude mice. This phenotype is accompanied by the upregulation of EMT-related genes Slug, Snail, TGFBR2, vimentin, N-cadherin, MMP-2, MMP-9, and MMP-14. However, these effects were not observed in the MCF-7 cells overexpressing FAM3B.
CONCLUSIONS: FAM3B overexpression contributes to tumor growth, promotion of metastasis, and, consequently, leads to a poor prognosis in the most aggressive forms of breast cancer. Future clinical research is necessary to validate FAM3B as both a diagnostic and a therapeutic strategy for TNBC.
摘要：
背景：三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型。FAM3B,分泌的蛋白质，已在各种类型的肿瘤中进行了广泛的研究。然而,它在乳腺癌中的功能仍然知之甚少。
方法：我们分析了来自TCGA数据库的乳腺癌患者的FAM3B表达数据，并使用Kaplan-Meier绘图仪分析了总生存期。转染MDA-MB-231TNBC肿瘤细胞系和激素响应性MCF-7细胞系以过表达FAM3B。我们评估了细胞死亡，致瘤性，通过MTT分析和体外侵袭性，流式细胞术测定，锚定非依赖性肿瘤生长，和伤口愈合试验，分别。我们通过裸鼠中的肿瘤异种移植物进行了体内评估。
结果：计算机模拟分析显示FAM3B在所有乳腺肿瘤中的表达较低。然而,FAM3B高表达的TNBC患者预后较差。FAM3B过表达保护MDA-MB-231细胞免于细胞死亡，随着Bcl-2和Bcl-xL的表达增加，和降低caspase-3活性。过表达FAM3B的MDA-MB-231细胞在体外也表现出增加的致瘤性和迁移率。在异种移植裸鼠中显示肿瘤生长增加和存活率降低。这种表型伴随着EMT相关基因Slug的上调，蜗牛,TGFBR2波形蛋白,N-钙黏着蛋白,MMP-2、MMP-9和MMP-14。然而,在过表达FAM3B的MCF-7细胞中未观察到这些作用。
结论：FAM3B过表达有助于肿瘤生长，促进转移，and,因此,在最具侵袭性的乳腺癌中导致预后不良。未来的临床研究有必要验证FAM3B作为TNBC的诊断和治疗策略。
方法：我们分析了来自TCGA数据库的乳腺癌患者的FAM3B表达数据，并使用Kaplan-Meier绘图仪分析了总生存期。转染MDA-MB-231TNBC肿瘤细胞系和激素响应性MCF-7细胞系以过表达FAM3B。我们评估了细胞死亡，致瘤性，通过MTT分析和体外侵袭性，流式细胞术测定，锚定非依赖性肿瘤生长，和伤口愈合试验，分别。我们通过裸鼠中的肿瘤异种移植物进行了体内评估。
结果：计算机模拟分析显示FAM3B在所有乳腺肿瘤中的表达较低。然而,FAM3B高表达的TNBC患者预后较差。FAM3B过表达保护MDA-MB-231细胞免于细胞死亡，随着Bcl-2和Bcl-xL的表达增加，和降低caspase-3活性。过表达FAM3B的MDA-MB-231细胞在体外也表现出增加的致瘤性和迁移率。在异种移植裸鼠中显示肿瘤生长增加和存活率降低。这种表型伴随着EMT相关基因Slug的上调，蜗牛,TGFBR2波形蛋白,N-钙黏着蛋白,MMP-2、MMP-9和MMP-14。然而,在过表达FAM3B的MCF-7细胞中未观察到这些作用。
结论：FAM3B过表达有助于肿瘤生长，促进转移，and,因此,在最具侵袭性的乳腺癌中导致预后不良。未来的临床研究有必要验证FAM3B作为TNBC的诊断和治疗策略。
