Reversal of the malignant phenotype of ovarian cancer A2780 cells through transfection with wild-type PTEN gene
Reversal of the malignant phenotype of ovarian cancer A2780 cells through transfection with wild-type PTEN gene
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转染野生型PTEN基因逆转卵巢癌A2780细胞的恶性表型
DOI：
10.1016/j.canlet.2008.06.018
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发表时间：
2008-11-28
期刊：
影响因子：
9.7
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Wu, Huijuan;Wang, Shixuan;Ma, Ding
目的：PTEN（10号染色体上磷酸酶和张力蛋白同源物缺失）是在人类染色体10q23上发现的抑癌基因。大量研究证明PTEN可以抑制多种癌细胞的增殖、迁移和侵袭。本研究的目的是确定转染野生型PTEN基因至卵巢癌细胞中上调PTEN基因是否可以抑制生长和迁移，探讨PTEN基因治疗卵巢癌的潜力。方法：将野生型和磷酸酶失活（C124A）PTEN质粒转染卵巢上皮癌A2780细胞，通过流式细胞术、TUNEL分析其对细胞凋亡、细胞增殖、细胞迁移和细胞侵袭的影响。结果：野生型和突变型PTEN均能显着上调PTEN基因的表达。然而，在卵巢癌细胞中，能够诱导细胞凋亡并减少细胞迁移、侵袭和增殖的是野生型PTEN，而不是磷酸酶失活的PTEN。结论：这些结果表明，PTEN依赖于其磷酸酶活性在细胞增殖、细胞迁移和侵袭中发挥重要作用。通过基因转移增强PTEN的表达足以逆转卵巢癌细胞的恶性表型，用野生型PTEN基因转染卵巢癌细胞可能是卵巢癌治疗干预的另一种新方法。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
Objective: PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor gene identified on human chromosome 10q23. Substantial studies have demonstrated that PTEN can inhibit cell proliferation, migration and invasion of many cancer cells. The purpose of this study was to determine whether upregulation of PTEN gene by transfection wild-type PTEN gene to ovarian cancer cells can inhibit growth and migration and to explore the potential for PTEN gene therapy of ovarian cancers.Method: Wild-type and phosphatase-inactive (C124A) PTEN plasmids were transfected into ovarian epithelial cancer A2780 cells, and their effects on cell apoptosis, cell proliferation, cell migration and cell invasion were analyzed by flow cytometry analysis, TUNEL assay, MTT assay, wound-healing assay and transwell assay.Results: Both wild-type and mutant PTEN can upregulate the expression of PTEN gene dramatically; however, it is wild-type PTEN not phosphatase-inactive PTEN that can induce apoptosis and decrease cell migration, invasion and proliferation in ovarian cancer cells.Conclusion: These results demonstrated that PTEN had played an important role in the cell proliferation, cell migration and invasion dependent on its phosphatase activity. Enhanced expression of PTEN by gene transfer is sufficient to reverse the malignant phenotype of ovarian cancer cells and transfection of ovarian cancer cells with wild-type PTEN gene might be another novel approach for therapeutic intervention in ovarian cancer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.