14-3-3 σ expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis.
14-3-3 σ expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis.
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DOI：
10.1371/journal.pone.0015864
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发表时间：
2011-01-10
期刊：
影响因子：
3.7
通讯作者：
Bishop AJ
中科院分区：
文献类型：
--
作者：
Ravi D;Chen Y;Karia B;Brown A;Gu TT;Li J;Carey MS;Hennessy BT;Bishop AJ
原代细胞的体外细胞培养实验表明，与生理氧气水平相比，在环境存在的情况下细胞增殖会受到抑制。癌症主要是一种异常细胞增殖的疾病，因此，研究在环境氧气下生长的癌细胞可能是不可取的。为了更好地了解 O2 对体外癌细胞增殖的影响，我们比较了一组卵巢癌细胞系在环境 (21%) 或生理 (3%) O2 下的生长潜力。我们的观察表明，与原代细胞类似，许多癌细胞对 O2 保持固有的敏感性，但有些细胞对 O2 浓度的变化不敏感。进一步的分析揭示了 G2/M 细胞周期转换调节缺陷与 14-3-3 σ 过度表达导致的 O2 不敏感性之间的关联。通过 RNAi 靶向 14-3-3 σ 过表达可恢复这些细胞系中的 O2 敏感性。此外，我们发现转移性卵巢肿瘤经常过度表达 14-3-3 σ，这与磷酸化 RB 结合，导致预后不良。癌细胞对氧气浓度的变化表现出不同的增殖敏感性。尽管尚未确定 O2 不敏感与转移之间的直接联系，但这项研究表明癌细胞中的 O2 不敏感表型与转移性肿瘤进展相关。
In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O2 levels. Cancer is primarily a disease of aberrant cell proliferation, therefore, studying cancer cells grown under ambient O2 may be undesirable. To understand better the impact of O2 on the propagation of cancer cells in vitro, we compared the growth potential of a panel of ovarian cancer cell lines under ambient (21%) or physiological (3%) O2. Our observations demonstrate that similar to primary cells, many cancer cells maintain an inherent sensitivity to O2, but some display insensitivity to changes in O2 concentration. Further analysis revealed an association between defective G2/M cell cycle transition regulation and O2 insensitivity resultant from overexpression of 14-3-3 σ. Targeting 14-3-3 σ overexpression with RNAi restored O2 sensitivity in these cell lines. Additionally, we found that metastatic ovarian tumors frequently overexpress 14-3-3 σ, which in conjunction with phosphorylated RB, results in poor prognosis. Cancer cells show differential proliferative sensitivity to changes in O2 concentration. Although a direct link between O2 insensitivity and metastasis was not determined, this investigation showed that an O2 insensitive phenotype in cancer cells to correlate with metastatic tumor progression.
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DOI：
10.1152/ajplung.00203.2002
发表时间：
2004-01-01
影响因子：
4.9
作者：
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