Fouz Nour, Amid Azura, Hashim Yumi Zuhanis Has-Yun
Bioprocess and Molecular Engineering Research Unit (BPMERU), Department of Biotechnology Engineering, Faculty of Engineering, International Islamic University Malaysia, P.O. Box 10, 50728, Kuala Lumpur, Malaysia,
Appl Biochem Biotechnol. 2014 Aug;173(7):1618-39. doi: 10.1007/s12010-014-0947-6. Epub 2014 Jun 14.
The contributing molecular pathways underlying the pathogenesis of breast cancer need to be better characterized. The principle of our study was to better understand the genetic mechanism of oncogenesis for human breast cancer and to discover new possible tumor markers for use in clinical practice. We used complimentary DNA (cDNA) microarrays to compare gene expression profiles of treated Michigan Cancer Foundation-7 (MCF-7) with recombinant bromelain and untreated MCF-7. SpringGene analysis was carried out of differential expression followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We identified 1,102 known genes differentially expressed to a significant degree (p<0.001) changed between the treatment. Within this gene set, 20 genes were significantly changed between treated cells and the control cells with cutoff fold change of more than 1.5. These genes are RNA-binding motif, single-stranded interacting protein 1 (RBMS1), ribosomal protein L29 (RPL29), glutathione S-transferase mu 2 (GSTM2), C15orf32, Akt3, B cell translocation gene 1 (BTG1), C6orf62, C7orf60, kinesin-associated protein 3 (KIFAP3), FBXO11, AT-rich interactive domain 4A (ARID4A), COPS2, TBPL1|SLC2A12, TMEM59, SNORD46, glioma tumor suppressor candidate region gene 2 (GLTSCR2), and LRRFIP. Our observation on gene expression indicated that recombinant bromelain produces a unique signature affecting different pathways, specific for each congener. The microarray results give a molecular mechanistic insight and functional effects, following recombinant bromelain treatment. The extent of changes in genes is related to and involved significantly in gap junction signaling, amyloid processing, cell cycle regulation by BTG family proteins, and breast cancer regulation by stathmin1 that play major roles.
乳腺癌发病机制背后的相关分子途径需要得到更好的描述。我们研究的原则是更好地理解人类乳腺癌发生的遗传机制,并发现可用于临床实践的新的潜在肿瘤标志物。我们使用互补DNA(cDNA)微阵列来比较经重组菠萝蛋白酶处理的密歇根癌症基金会-7(MCF-7)细胞和未经处理的MCF-7细胞的基因表达谱。对差异表达进行SpringGene分析,随后进行 Ingenuity 通路分析(IPA),以了解疾病和病症发展中的潜在后果。我们鉴定出1102个已知基因在处理之间有显著差异表达(p<0.001)。在这个基因集中,有20个基因在处理细胞和对照细胞之间有显著变化,截断倍数变化超过1.5。这些基因是RNA结合基序单链相互作用蛋白1(RBMS1)、核糖体蛋白L29(RPL29)、谷胱甘肽S-转移酶μ2(GSTM2)、C15orf32、Akt3、B细胞易位基因1(BTG1)、C6orf62、C7orf60、驱动蛋白相关蛋白3(KIFAP3)、FBXO11、富含AT的相互作用结构域4A(ARID4A)、COPS2、TBPL1|SLC2A12、TMEM59、SNORD46、胶质瘤肿瘤抑制候选区域基因2(GLTSCR2)和LRRFIP。我们对基因表达的观察表明,重组菠萝蛋白酶产生了影响不同途径的独特特征,每种同源物都具有特异性。微阵列结果提供了重组菠萝蛋白酶处理后的分子机制见解和功能效应。基因变化的程度与缝隙连接信号传导、淀粉样蛋白加工、BTG家族蛋白对细胞周期的调节以及stathmin1对乳腺癌的调节密切相关且起着重要作用。