Notch1信号通路在乳腺癌中的研究进展

Progress in the study of Notch1 signaling pathway in breast cancer

乳腺癌是女性最常见、死亡率最高的恶性肿瘤之一,近年来其发病率不断升高。研究发现Notch1信号通路在乳腺癌中起着重要的作用。研究发现Notch1在正常乳腺组织和乳腺良性病变以及乳腺癌中均有表达,在乳腺浸润性导管癌中的表达率明显高于导管原位癌,其表达与乳腺癌HER-2亚型有关,在HER-2阳性型中的Notch1的阳性表达率明显高于其他亚型。研究认为Notch1阳性表达率高与其乳腺癌的分化程度低、分期晚、淋巴结转移阳性率高以及脑转移有关,预示着乳腺癌的预后差,并被认为可作为判断预后的临床指标。此外研究发现Notch1的高表达可导致乳腺癌对阿霉素与紫杉醇的耐药。研究发现Notch1高表达与乳腺癌侵袭强、凋亡抑制有关。研究还发现Notch1的表达影响乳腺癌干细胞的数量,是维持乳腺癌干细胞恶性表型的重要因子。且Notch1与VEGF、c-myc、CCL2、TRB3、MMP2等相关基因表达及肿瘤微环境相关。针对Notch1的靶向治疗的研究有Notch1单克隆抗体、三氧化二砷以及金雀异黄素等药物,以及Notch1相关通路的靶向治疗药物,均可抑制乳腺癌细胞的生长,对乳腺癌有抗肿瘤作用。

Breast cancer is one of the most common malignant tamors in women with the highest death rate. The incidence has been going up in these years. Studies have found that Notchl signaling pathway plays an important role in breast cancer and is expressed in normal breast tissue and breast benign lesions as well as breast cancer, and the expression rate in breast invasive ductal carcinoma is significantly higher than that of ductal carcinoma in situ. The expression of Notchl in breast cancer is associated with breast cancer subtype HER-2 and the positive expression rate of Notchl is significantly higher in HER-2 positive subtype than in other subtypes. Studies have suggested that high expression rate of Notchl in breast cancer is associated with the low degree of differentiation of breast cancer and late staging, lymph node metastasis rate, and brain metastasis, indicating poor prognosis, and is considered as a clinical prognostic indicator. Besides, it was also found that high expression of Notchl could cause breast cancer resistance to doxorubicin and paclitaxel and high expression of Notchl signifies breast cancer invasion and inhibition of apoptosis. The expression of Notchl was also found to influence the number of breast cancer stem cells and act as the important factor to maintain the malignant phenotype of breast cancer stem ceils. Notch1 signaling pathway is related with VEGF, c-myc, CCL2, TRB3, MMP2 and other relevant tumor microenvironments. There Notehl monoclonal antibodies, arsenic trioxide and genistein and other drugs, as well as drugs related to Notchl pathway targeted therapies, may inhibit the growth of breast cancer cells and has important anti-tumor effect.