Champine Patricia J, Michaelson Jacob, Weimer Bart C, Welch Danny R, DeWald Daryll B
Center for Integrated BioSystems, Utah State University, Logan, UT 84322-4700, USA.
Clin Exp Metastasis. 2007;24(7):551-65. doi: 10.1007/s10585-007-9092-8. Epub 2007 Sep 25.
We used Affymetrix microarrays to compare gene expression profiles of the metastatic parental breast cancer cell line MDA-MB-435 (435) and the non-metastatic daughter cell line created by the stable expression of the BReast cancer Metastasis Suppressor 1 (BRMS1) gene in 435 cells, MDA-MB-435-BRMS1 (435/BRMS1). Analysis of microarray data provided insight into some of the potential mechanisms by which BRMS1 inhibits tumor formation at secondary sites. Furthermore, due to the importance of the microenvironment, we also examined gene expression under different growth conditions (i.e., plus or minus serum). Expression of 565 genes was significantly (adjusted P-value <0.05) altered regardless of in vitro growth conditions. BRMS1 expression significantly increased multiple major histocompatability complex (MHC) genes and significantly decreased expression of several genes associated with protein localization and secretion. The pattern of gene expression associated with BRMS1 expression suggests that metastasis suppression may be mediated by enhanced immune recognition, altered transport, and/or secretion of metastasis-associated proteins.
我们使用Affymetrix微阵列来比较转移性亲代乳腺癌细胞系MDA-MB-435(435)和通过在435细胞中稳定表达乳腺癌转移抑制因子1(BRMS1)基因而产生的非转移性子代细胞系MDA-MB-435-BRMS1(435/BRMS1)的基因表达谱。对微阵列数据的分析深入了解了BRMS1抑制肿瘤在继发部位形成的一些潜在机制。此外,由于微环境的重要性,我们还研究了不同生长条件下(即有血清或无血清)的基因表达。无论体外生长条件如何,565个基因的表达均有显著改变(校正P值<0.05)。BRMS1的表达显著增加了多个主要组织相容性复合体(MHC)基因,并显著降低了与蛋白质定位和分泌相关的几个基因的表达。与BRMS1表达相关的基因表达模式表明,转移抑制可能是由增强的免疫识别、转移相关蛋白转运和/或分泌的改变介导的。