Boulaiz Houria, Alvarez Pablo J, Prados Jose, Marchal Juan, Melguizo Consolación, Carrillo Esmeralda, Peran Macarena, Rodríguez Fernando, Ramírez Alberto, Ortíz Raúl, Aránega Antonia
Basic Cardiovascular Research Section, Department of Anatomy and Human Embriology, School of Medicine, University of Granada, Granada E-18012, Spain; E-Mails:
Int J Mol Sci. 2011;12(11):7445-58. doi: 10.3390/ijms12117445. Epub 2011 Oct 31.
Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.
在过去几十年中，乳腺癌研究发展迅速，使得患者的生存时间延长，并为开发晚期乳腺癌的治愈性疗法开辟了可能性。我们对与乳腺癌进展和发展相关的生物学途径的了解不断增加，再加上传统治疗方法的失效，促使我们探索基因治疗作为一种替代治疗策略。我们之前报道过，来自大肠杆菌的gef基因在乳腺癌细胞中显示出相当大的细胞毒性作用。然而，其作用机制尚未阐明。使用流式细胞术和免疫细胞化学分析的间接免疫荧光技术用于检测乳腺癌标志物：雌激素（ER）和孕激素（PR）激素受体、人表皮生长因子受体-2原癌基因（c-erbB-2）、ki-67抗原和p53蛋白。gef基因诱导ER和PR表达增加，ki-67和c-erbB-2基因表达减少，表明预后更好、对治疗的反应更好、无病生存期和生存期更长。它还增加了p53表达，表明gef诱导的细胞凋亡受p53介导的信号通路调节。这些发现支持了gef基因提供了一种乳腺癌基因治疗新方法的假设。
