Department of Pancreatic and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Int J Oncol. 2013 Oct;43(4):1219-27. doi: 10.3892/ijo.2013.2029. Epub 2013 Jul 23.
Breast cancer is the most frequently diagnosed cancer in women. In these studies, a metastasis suppressor gene, KISS1 and its truncated fragment, were overexpressed in the breast cancer cell line MDA-MB-231. In addition, KISS1 expression was downregulated in MDA-MB-157 cell line using a KISS1-specific siRNA. The effects of KISS1 on breast cancer cells both in vivo and in vitro were then identified. Our results indicate that KISS1 can induce apoptosis and inhibit mobility of breast cancer cells. Moreover, the expression of KISS1 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher compared to that of mice bearing tumors that did not express KISS1. We also confirm that KISS1 could decrease the number of circulating tumor cells (CTCs). The plasma levels of metastin and the number of CTCs were significantly positively correlated. Furthermore, we found that KISS1 can inactivate p-MEK and p-ERK. Overall, these studies demonstrate the antitumor activity of KISS1 in the breast cancer cell lines and provide insight into relevant mechanisms that may lead to novel treatments for breast cancer.
乳腺癌是女性最常见的癌症。在这些研究中,转移抑制基因 KISS1 及其截断片段在乳腺癌细胞系 MDA-MB-231 中过表达。此外,使用 KISS1 特异性 siRNA 下调 MDA-MB-157 细胞系中的 KISS1 表达。然后在体内和体外鉴定 KISS1 对乳腺癌细胞的影响。我们的结果表明,KISS1 可诱导乳腺癌细胞凋亡并抑制其迁移。此外,在已建立的异种移植肿瘤中 KISS1 的表达与肿瘤体积和重量的减少相关。因此,与不表达 KISS1 的肿瘤相比,这些小鼠的存活率明显更高。我们还证实 KISS1 可以减少循环肿瘤细胞 (CTC) 的数量。血浆中 metastin 的水平与 CTC 的数量呈显著正相关。此外,我们发现 KISS1 可以使 p-MEK 和 p-ERK 失活。总的来说,这些研究表明 KISS1 在乳腺癌细胞系中具有抗肿瘤活性,并为可能导致乳腺癌新治疗方法的相关机制提供了新的见解。