Departments of Medical Oncology, Beckman Research Institute of City of Hope, Comprehensive Cancer Center and National Medical Center, Duarte, CA 91010, United States.
Departments of Medical Oncology, Beckman Research Institute of City of Hope, Comprehensive Cancer Center and National Medical Center, Duarte, CA 91010, United States; Departments of Molecular Medicine, Beckman Research Institute of City of Hope, Comprehensive Cancer Center and National Medical Center, Duarte, CA 91010, United States.
J Proteomics. 2019 Feb 10;192:233-245. doi: 10.1016/j.jprot.2018.09.005. Epub 2018 Sep 21.
In spite of rapid advances in understanding of signaling networks associated with the incidence and therapeutic-sensitivity, breast cancer (BC) still remains the most commonly diagnosed and prevalent cancer in women. Emergence of resistance to hormonal interventions in estrogen-receptor (ER) positive BC coupled to loss of ER expression and activation of ER-independent growth factor, heat-shock, MYC and WNT pathways along with distinct mechanisms of therapeutic-resistance in HER2 over-expressing and triple-negative subtypes of BC collectively necessitates deeper profiling of the mechanistic networks regulated by potential lead anticancer compounds intended for further development to target BC. A significant part of the search for novel lead anticancer compounds for BC has focused on phytochemicals including flavonoids found in citrus fruits, which have shown promising anticancer activity. Based on the initial studies which revealed the anticancer effect of 2HF in BC, we employed an advanced TMT 10plex labeled proteomic approach to characterize the changes in non-phosphorylated and phosphorylated proteomic profile of ER MCF7, triple-negative MDA-MB231 and HER2 SKBR3 BC cells, and MCF10A normal breast epithelial cells. 2HF induced significant changes in the proteins responsible for BC incidence, metastases and therapeutic sensitivity in BC cells.
尽管在理解与乳腺癌发生和治疗敏感性相关的信号转导网络方面取得了快速进展，但乳腺癌仍然是女性中最常见的诊断和流行癌症。与雌激素受体 (ER) 阳性乳腺癌中激素干预的耐药性的出现、ER 表达的丧失以及 ER 独立生长因子、热休克、MYC 和 WNT 通路的激活相关，再加上 HER2 过表达和三阴性乳腺癌亚型中独特的治疗耐药机制，共同需要对潜在的抗癌先导化合物调节的机制网络进行更深入的分析，以进一步开发针对乳腺癌的靶点。寻找新型乳腺癌抗癌先导化合物的研究重点很大一部分集中在植物化学物质上，包括柑橘类水果中的类黄酮，它们表现出有希望的抗癌活性。基于最初的研究揭示了 2HF 在乳腺癌中的抗癌作用，我们采用了先进的 TMT 10plex 标记蛋白质组学方法来描述 ER MCF7、三阴性 MDA-MB231 和 HER2 SKBR3 乳腺癌细胞以及 MCF10A 正常乳腺上皮细胞中非磷酸化和磷酸化蛋白质组图谱的变化。2HF 在乳腺癌细胞中诱导了与乳腺癌发生、转移和治疗敏感性相关的蛋白质的显著变化。
