Ectopic expression of RhoBTB2 inhibits migration and invasion of human breast cancer cells
Ectopic expression of RhoBTB2 inhibits migration and invasion of human breast cancer cells
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DOI：
10.4161/cbt.10.11.13431
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发表时间：
2010-12-01
影响因子：
3.6
通讯作者：
Wang, Shui
中科院分区：
文献类型：
--
作者：
Ling, Li-Jun;Lu, Chao;Wang, Shui
RhoBTB 2，又称乳腺癌2（DBC 2）基因，是一个编码小GTP酶的新基因家族的非典型成员，被认为是乳腺癌和其他人类恶性肿瘤的候选抑癌基因。在本研究中，我们发现RhoBTB 2的异位表达以剂量依赖的方式抑制人转移性乳腺癌细胞系MDA-MB-231和MDA-MB-435的迁移和侵袭。蛋白质印迹分析显示，RhoBTB 2的异位表达诱导乳腺癌转移抑制因子BRMS 1的显著增加。BRMS 1表达的siRNA抑制显著逆转了RhoBTB 2对两种细胞系迁移和侵袭能力的抑制作用。Ezrin是ezrin-radixin-moesin细胞凋亡相关蛋白家族的成员，是调节癌症迁移和侵袭的关键信号分子。Western blotting分析表明RhoBTB 2的异位表达导致MDA-MB-231和MDA-MB-435细胞中ezrin和Akt 2的磷酸化降低。因此，我们得出结论，乳腺癌转移抑制BRMS 1的上调和癌症转移相关基因ezrin的磷酸化的下调有助于RhoBTB 2诱导的转移性乳腺癌细胞迁移和侵袭的抑制。我们的研究结果表明，了解RhoBTB 2介导的迁移和抑制侵袭对于开发旨在预防和治疗乳腺癌转移患者的新疗法至关重要。
RhoBTB2, or Deleted in Breast Cancer 2 (DBC2), identified as a candidate tumor suppressor gene for breast cancer and other human malignancies, is an atypical member of a novel gene family encoding small GTPases. In this study, we found that ectopic expression of RhoBTB2 inhibits the migration and invasion of the human metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435 in a dose-dependent manner. Western blotting analysis revealed that ectopic expression of RhoBTB2 induces a significant increase in the breast cancer metastasis suppressor, BRMS1. siRNA suppression of BRMS1 expression markedly reversed the inhibitory effects of RhoBTB2 on the migration and invasion abilities of both cell lines. Ezrin is a member of the ezrin-radixin-moesin cytoskeleton-associated protein family and is a key signaling molecule that regulates cancer migration and invasion. Western blotting analysis demonstrated that ectopic expression of RhoBTB2 results in decreased phosphorylation of ezrin and Akt2 in both MDA-MB-231 and MDA-MB-435 cells. Therefore, we conclude that up-regulation of the breast cancer metastasis suppressor BRMS1 and down-regulation of the phosphorylation of the cancer metastasis-related gene, ezrin, contributed to RhoBTB2-induced inhibition of metastatic breast carcinoma cell migration and invasion. Our findings suggest that understanding RhoBTB2-mediated migration and suppression of invasion is critical to the development of new therapies designed to prevent and treat patients with breast cancer metastasis.