Yin Y X, Shen F, Pei H, Ding Y, Zhao Hua, Zhao Min, Chen Q
Wuxi Maternity and Children Health Hospital, Nanjing Medical University, Wuxi, China.
Tumour Biol. 2012 Oct;33(5):1581-7. doi: 10.1007/s13277-012-0412-5. Epub 2012 May 30.
Breast cancer is the most common cancer in women worldwide. Studies have suggested that Ras-related protein 25 (Rab25), a member of Rab small GTPase family, is involved in the pathogenesis of breast cancer. In this study, we investigated whether the expression of Rab25 correlated with lymphatic metastasis in breast cancer and whether the expression of Rab25 was positively correlated with oestrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer. Breast cancer tissues from 42 invasive ductal breast cancer patients with or without lymphatic metastasis were collected and the levels of Rab25 mRNA and protein measured by quantitative real-time PCR and immunohistochemistry, respectively. The mRNA level of Rab25 was significantly increased in invasive ductal breast cancer with lymphatic metastasis compared to that in invasive ductal breast cancer without lymphatic metastasis. Immunohistochemical analysis demonstrated that Rab25 and vascular endothelial growth factor (VEGF) were highly expressed in invasive ductal breast cancer with lymphatic metastasis regardless of whether the cancer is ER and PR positive or negative. Higher expression of Rab25 positively correlated with VEGF expression. However, the expressions of Rab25 in ER and PR-positive cancers were much higher than ER and PR-negative cancers regardless of whether lymphatic metastasis occurred. These data suggest that higher level of Rab25 was associated with lymphatic metastasis, specifically in ER and PR-positive breast cancer. The better understanding of the mechanism of Rab25 may provide a basis for the development of a novel therapeutic target in breast cancer.
乳腺癌是全球女性中最常见的癌症。研究表明,Ras相关蛋白25(Rab25)作为Rab小GTP酶家族的一员,参与了乳腺癌的发病机制。在本研究中,我们调查了Rab25的表达是否与乳腺癌的淋巴转移相关,以及Rab25的表达是否与乳腺癌中的雌激素受体(ER)和孕激素受体(PR)表达呈正相关。收集了42例有或无淋巴转移的浸润性导管癌患者的乳腺癌组织,并分别通过定量实时PCR和免疫组织化学法检测Rab25 mRNA和蛋白水平。与无淋巴转移的浸润性导管癌相比,有淋巴转移的浸润性导管癌中Rab25的mRNA水平显著升高。免疫组织化学分析表明,无论癌症是ER和PR阳性还是阴性,Rab25和血管内皮生长因子(VEGF)在有淋巴转移的浸润性导管癌中均高表达。Rab25的高表达与VEGF表达呈正相关。然而,无论是否发生淋巴转移,Rab25在ER和PR阳性癌症中的表达均远高于ER和PR阴性癌症。这些数据表明,Rab25水平升高与淋巴转移相关,特别是在ER和PR阳性的乳腺癌中。对Rab25机制的更好理解可能为乳腺癌新治疗靶点的开发提供依据。