Metastasis and Angiogenesis Research Group, CUPUCI, Cardiff University School of Medicine, Henry Welcome Building, Heath Park, Cardiff CF14 4XN, U.K.
Anticancer Res. 2014 Mar;34(3):1417-26.
Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers.
BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Human breast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored.
BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (p<0.05). Blocking phospholipase-Cγ (PLCγ) had a significant influence on the BRMS-1-induced cell migration. Finally, significantly low levels of BRMS1 were observed in patients with high-grade tumors (p=0.12), in patients with distant metastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035).
BRMS-1 is aberrantly expressed in human breast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.
乳腺癌转移抑制因子-1（BRMS1）是候选转移抑制基因，已显示出在不同肿瘤类型中，包括非小细胞肺癌、卵巢癌、黑色素瘤和乳腺癌中，具有抑制肿瘤进展而不阻止原位肿瘤生长的潜力。
在乳腺癌样本组织中定量检测 BRMS-1 基因转录本，并分析其与组织学和临床患者预后的关系。使用人乳腺癌细胞系 MDA MB-231 和 MCF-7 对 BRMS-1 的表达进行基因修饰，并在 BRMS-1 修饰后测试生物学反应。还探索了受 BRMS-1 影响的关键候选信号通路。
BRMS1 存在于 MDA MB-231 和 MCF-7 细胞系中。使用抗 BRMS1 转基因，我们在两种细胞中均在 mRNA 和蛋白水平下调 BRMS1 的转录本。与各自的野生型和对照细胞相比，BRMS1 的敲低使两种细胞的细胞生长速度更快，细胞迁移和侵袭速度更快（p<0.05）。阻断磷脂酶 Cγ（PLCγ）对 BRMS-1 诱导的细胞迁移有显著影响。最后，在高级别肿瘤患者（p=0.12）、远处转移患者（p=0.05）和死于乳腺癌的患者（p=0.0037）中观察到 BRMS1 的水平显著降低。此外，BRMS1 水平低的患者总生存期明显缩短（p=0.035）。
BRMS1 在人乳腺癌中异常表达，与疾病进展和患者生存呈负相关。这可能是通过其对乳腺癌细胞侵袭和迁移的影响发生的。
