信号转导和转录激活因子5与β-catenin在乳腺癌组织中的表达及其临床意义

Expression of STAT5 and β-catenin in human breast carcinoma and its clinical significance

背景与目的:从信号传导途径治疗疾病是目前生物治疗的新兴领域。有目的地控制信号分子的传递,有可能为诊治人类重大疾病开辟新的途径。β-caten in作为一种原癌蛋白是W nt信号系统下游的关键成分,它参与由E-cadherin介导的细胞间的信号传导和细胞黏附。信号传导和转录激活因子5(signal transducers and acti-vators of transcription 5,STAT5)是细胞浆转录因子,最初发现在小鼠乳腺发育过程中,因为参与正常乳腺上皮细胞的生长和发育,又称乳腺生长因子。W nt信号途径和STAT5信号途径是在细胞的正常生长发育过程中起重要作用的二条信号途径,它们的异常调节可引起生物发育缺陷,并参与肿瘤的发生。乳腺癌是我国女性高发性恶性肿瘤,分布广泛,但其发生的分子机制尚不明确。目前国内外对两者在乳腺癌中的情况未见报道。因此,研究STAT5和β-caten in在乳腺癌中的表达及其临床意义是本文关注的重点,目的是为了找到诊断和治疗乳腺癌的新分子靶点。方法:采用免疫组化S-P法检测20例正常乳腺组织和72例乳腺癌组织中STAT5和-βcaten in的表达情况。结果:STAT5和β-caten in在20例正常乳腺组织中均为阴性表达,而在乳腺癌组织中的阳性表达率分别是65.3%和70.8%;两者的表达水平均与乳腺癌临床分期、病理组织学分级及淋巴结转移有关(P<0.05);而与患者年龄及组织学类型无关(P>0.05)。STAT5和-βcaten in在乳腺癌组织中的阳性表达呈显著正相关(r=0.56,P<0.01)。结论:STAT5和-βcaten in在乳腺癌的阳性表达可能在乳腺癌的发生和侵袭转移中起重要作用,联合检测STAT5和β-caten in可以作为乳腺癌的诊断和预后判断指标。

Background and purpose： It is a new area of biologic treatment which treated tumor from signal transducer pathway at present. In recent studies, β-catenin played a critical role in the E-cadherin mediated intercellular signal transduction and cell adhesion. Loss of normal cellular adhesion play an importand role in many aspects of tumor bilogy. It served as a oneoprotein of downstream in Wnt signal pathway. Disovered originally as a mammary gland factor（ MGF）, signal transducers and activators of transcription（STAT） 5 plays the most prominent role of all STAT family members during the mouse mammary gland development. STAT5 is implicated as important regulators of the development and differentiation of mulicellular organism. In many tumors, the abnormal regulation of β-catenin and STAT5 could arouse deficiency of biologic development, and be concered with the tumor progression. Only limited information is available, however, on the expression and cell localization of β-catenin and STAT5 in human breast cancers, and the molecular changes leading to mammary cell transformation remain largely unknown. We selected β-catenin and STAT5 as research objects and investigated the expression of STAT5 and β-catenin , and their clinical significance in breast carcinoma. As its role in human breast cancer progression and development is defined, β-catenin and STATS could become the new molecular target for breast carcinoma therapy. Methods： Expression of STATS and β-catenin were examined by immunohistochemistry SP method in 20 specimens of normal breast tissue and 72 specimens of breast carcinoma. Results： The negative rates of STATS and [3-catenin in normal breast tissue were 100 %, but the positive rates of STATS and β-catenin in breast carcinoma were 65.3 %, 70.8 % respectively. The expression of STATS and β-catenin were correlated significantly with clinical stage, histological grading and lymph nodes metastases（ P 〈 0.05） ; while no significant association was found with patient age and histological types（ P 〉 0.05）. In breast carcinoma, STATS was positively correlated with the expression of β-catenin（ r = 0.56, P 〈0.01）. Conclusions： Overexpression of STATS and β-catenin in breast carcinoma may play an important role in the oncogenesis and metastasis of breast cancer. The associated detection of STATS and β-catenin may be a useful maker for accurately predicting diagnosis and prognosis.