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BRCA1抑制黄体酮刺激乳腺癌细胞增殖和迁移
  • ISSN号:1673-4254
  • 期刊名称:《南方医科大学学报》
  • 时间:0
  • 分类:R737.9[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]南方医科大学基础医学院细胞生物学教研室,广东广州510515, [2]湖南省湘潭市中心医院生殖与遗传中心,湖南湘潭411100
  • 相关基金:国家自然科学基金(30470673,81071810)
中文摘要:

目的研究BRCA1是否可以调节黄体酮刺激乳腺癌细胞增殖和迁移。方法乳腺癌细胞MCF-7和T-47D转染质粒过表达BRCA1或转染相应空质粒作对照,并以黄体酮刺激乳腺癌细胞,观察过表达BRCA1对黄体酮刺激乳腺癌细胞增殖和迁移的影响;MCF-7细胞转染siRNA敲低BRCA1或转染杂乱siRNA作为对照,并加黄体酮刺激乳腺癌细胞,观察敲低BRCA1对黄体酮刺激乳腺癌细胞增殖和迁移的影响;用MTT实验结果计算细胞增殖率,用“划痕愈合实验”结果计算细胞迁移率。结果黄体酮刺激并转染空质粒对照组或过表达BRCA1组:细胞增殖率,MCF-7细胞分别是(114.4±6.0)%和(82.1±3.2)%,T47-D细胞分别是(111.3±4.3)%和(84.2±3.5)%,两组间细胞增殖率差异均有统计学意义(P〈0.05);细胞迁移率,MCF-7细胞分别是55.9%和15.8%,T-47D分别是44.83%和10.43%。加黄体酮刺激并转染杂乱siRNA或BRCAlsiRNAMCF-7:细胞增殖率分别是(114.4±3.05)%和(125.3±4.0)%,两组间差异有统计学意义(P〈0.05);细胞迁移率分别是39.2%和69.08%。黄体酮受体拮抗剂RU486可以拮抗敲低BRCA1增强黄体酮促进乳腺癌细胞增殖和迁移。结论散炭性乳腺癌可能因其BRCA1低表达而使黄体酮对乳腺癌细胞的增殖和迁移作用增强。

英文摘要:

Objective To study the effect of BRCA1 in regulating the proliferation and migration of breast cancer ceils stimulated by progesterone. Methods Breast cancer MCF-7 and T-47D cell were transfected with a vector containing the coding sequence of BRCA1 (pFlag-CMV2-BRCA1 wt) to induce BRCA1 overexpression or with the empty vector (control). The cells were then stimulated with progesterone, and the cell proliferation and migration were observed using MTT assay and wound healing assay, respectively. The proliferation and migration of MCF-7 cells were also observed following transfection with a small interfering RNA (siRNA) for BRCA1 knockdown or with a scrambled siRNA prior to progesterone stimulation. Results Transfection with the empty vector and with pFlag-CMV2-BRCA1 wt prior to progesterone stimulation caused significantly different proliferation rates in MCF-7 cells [(114.4±6.0)% vs (82.1±3.2)%, P〈0.05] and in T-47D cells [(111.3±4.3)% vs (84.2±3.5)%, P〈0.05], resulting also in significantly different cell migration rates (55.9% vs 15.8% in MCF-7 cells and 44.83% vs 10.43% in T-47D cells). Compared to the scrambled siRNA, BRCA1 siRNA transfection prior to progesterone stimulation significantly increased the proliferation rates [(114.4±3.05)% vs (125.3±4.0)%, P〈0.05] and migration rate (39.2% vs 69.08%) of MCF-7 cells. The progesterone antagonist RU468 could antagonize the effects of BRCA1 knockdown in enhancing progesterone-stimulated MCF-7 cell proliferation and migration. Conclusions A decreased BRCA1 expression can enhance progesterone-stimulated tumor cell proliferation and migration in sporadic breast cancer.

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期刊信息
  • 《南方医科大学学报》
  • 中国科技核心期刊
  • 主管单位:广东省教育厅
  • 主办单位:南方医科大学
  • 主编:陈敏生
  • 地址:广州市广州大道北1838号
  • 邮编:510515
  • 邮箱:xbbjb@fimmu.com
  • 电话:020-61648175 61647352
  • 国际标准刊号:ISSN:1673-4254
  • 国内统一刊号:ISSN:44-1627/R
  • 邮发代号:46-10
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:25001