Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer.
Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer.
复制标题
DOI：
10.1038/sj.bjc.6602029
复制
发表时间：
2004-08-31
影响因子：
8.8
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Sagara, Y;Mimori, K;Yoshinaga, K;Tanaka, F;Nishida, K;Ohno, S;Inoue, H;Mori, M
Caveolin-1和Caveolin-2（CAV 1、CAV 2）是位于7 q31脆性区（FRA 7 G）的紧密连锁基因，并且已经报道了涉及该区域的杂合性丢失在乳腺癌中。一些研究表明，CAV 1是体外HER 2/neu信号转导的负调节因子。然而，CAV 1在乳腺癌中的临床意义尚未明确。应用实时荧光定量PCR技术检测了162例乳腺癌组织中CAV 1、CAV 2和HER 2/neu的mRNA水平。免疫印迹和免疫组化检测Caveolin-1和Caveolin-2蛋白表达。然后，我们评估了162例乳腺癌病例中CAV 1、CAV 2和HER 2/neu基因表达与临床病理因素之间的相关性。结果显示，乳腺癌组织中HER 2/neu mRMA的表达明显高于癌旁正常组织（P <0.001），而CAV 1和CAV 2 mRMA的表达明显低于癌旁正常组织（P<0.001）。与正常组织相比，通过Western印迹法，癌组织中的小窝蛋白-1和-2蛋白表达水平也被抑制。免疫组化结果显示，CAV 1和CAV 2蛋白在乳腺肌上皮细胞中表达丰富，而在导管上皮细胞中表达较弱。CAV 1 mRNA水平降低与肿瘤大小增加（P=0.041）和雌激素受体阴性（P=0.021）显著相关。CAV 2 mRNA水平低与孕酮受体阴性（P=0.013），HER 2/neu mRNA水平高与激素受体阴性（ER，P=0.029，PgR，P=0.019）。而HER 2/neu和CAV 1 mRNA水平之间无相关性，CAV 1和CAV 2 mRNA水平之间观察到显著相关性（P<0.001）。我们的研究结果表明，CAV 1抑制密切相关的CAV 2在乳腺癌中，CAV 1水平与肿瘤大小呈负相关，CAV 1和CAV 2水平与激素受体状态。因此，CAV 1和CAV 2在乳腺癌患者的肿瘤进展中起重要作用。
Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/neu signal transduction in vitro. However, the clinical significance of CAV1 in breast cancer has not yet been clarified. We examined quantitatively the mRNA levels of CAV1, CAV2 and HER2/neu in 162 cases of breast cancer using real-time PCR. Caveolin-1 and -2 protein expression was also examined by Western blotting and immunohistochemistry. We then evaluated for correlations between CAV1, CAV2 and HER2/neu gene expression and clinicopathologic factors in the 162 breast cancer cases. Results showed higher HER2/neu mRMA levels and lower CAV1 and CAV2 mRMA levels in breast cancer tissues than in corresponding normal tissues (P<0.001). Caveolin-1 and -2 protein expression levels were also suppressed in cancer tissues compared to normal tissues by Western blotting. Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells. Reduced CAV1 mRNA level was significantly associated with increasing tumour size (P=0.041), and negative oestrogen receptor status (P=0.021). There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P=0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P=0.029, PgR, P=0.019). While there was no relationship between HER2/neu and CAV1 mRNA levels, a significant association between CAV1 and CAV2 mRNA levels was observed (P<0.001). Our results indicated that CAV1 suppression correlated closely with that of CAV2 in breast cancer, that CAV1 level was inversely correlated with tumour size, and that CAV1 and CAV2 levels were correlated with hormonal receptor status. Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients.
登录
查看更多内容
影响因子：
4.4
作者：
Tatarelli, C;Linnenbach, A;Croce, CM
通讯作者：
Croce, CM
影响因子：
4.7
作者：
Davidson, B;Nesland, JM;Reich, R
通讯作者：
Reich, R
影响因子：
4.8
作者：
Kim, YN;Wiepz, GJ;Bertics, PJ
通讯作者：
Bertics, PJ
影响因子：
8
作者：
Lee, SW;Reimer, CL;Schnitzer, JE
通讯作者：
Schnitzer, JE
影响因子：
6
作者：
Wiechen, K;Sers, C;Schneider, U
通讯作者：
Schneider, U