Expression of calbindin-D28k is inversely correlated with proapototic gene expression in hydrogen peroxide-induced cell death in endometrial cancer cells.
Expression of calbindin-D28k is inversely correlated with proapototic gene expression in hydrogen peroxide-induced cell death in endometrial cancer cells.
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DOI：
10.3892/ijo.2011.916
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发表时间：
2011-04
影响因子：
5.2
通讯作者：
E. Jung;Kyung-Chul Choi;E. Jeung
中科院分区：
文献类型：
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作者：
E. Jung;Kyung-Chul Choi;E. Jeung
Calbindin-D28k (CaBP-28k) 是一种钙结合蛋白，对于细胞内 Ca2+ 缓冲非常重要，并且已知在神经元、成骨细胞和雄性生殖细胞中具有抗凋亡特性。尽管子宫内膜癌是一种常见的侵袭性妇科恶性肿瘤，但子宫 CaBP-28k 在子宫内膜癌细胞凋亡信号传导中的作用尚不清楚。本研究探讨了 CaBP-28k 在过氧化氢 (H2O2) 诱导的人子宫内膜 Ishikawa 细胞凋亡信号中的作用。通过蛋白质印迹分析评估 H2O2 对 Bax、p53 和 Bcl-2 表达的剂量和时间依赖性影响。用 1 mM H2O2 处理细胞 1 小时，诱导 Bax 和 p53 表达增加，但 Bcl-2 的表达不受 H2O2 处理的影响。有趣的是，在 H2O2 诱导的细胞凋亡过程中，CaBP-28k 的过表达抑制细胞死亡，并导致 Bax、p53 和 caspase 3 表达下降，表明 CaBP-28k 阻断细胞凋亡相关基因表达的上调。 CaBP-28k 的 siRNA 敲低导致 H2O2 诱导的细胞死亡增加，以及 Bax、p53 和 caspase 3 的增加，这提供了额外的证据，表明 CaBP-28k 基因的诱导可能与 H2O2 介导的细胞死亡过程中的生存信号相关。总体而言，这些结果表明 CaBP-28k 表达与人子宫内膜 Ishikawa 细胞中促凋亡基因表达呈负相关。
Calbindin-D28k (CaBP-28k) is a calcium binding protein important for intracellular Ca2+ buffering and known to have anti-apoptotic properties in neurons, osteoblasts and male germ cells. Although endometrial cancer is a common invasive gynecologic malignancy, the involvement of uterine CaBP-28k in apoptotic signaling of endometrial cancer is poorly understood. The present study investigates the role of CaBP-28k in hydrogen peroxide (H2O2)-induced apoptotic signaling in human endometrial Ishikawa cells. The dose- and time-dependent effect of H2O2 on Bax, p53 and Bcl-2 expression was assessed by Western blot analysis. Treatment of cells with 1 mM H2O2 for 1 h induced an increase in Bax and p53 expression, but the expression of Bcl-2 was not affected by H2O2 treatment. Interestingly, overexpression of CaBP-28k inhibited cell death and caused a decrease in Bax, p53 and caspase 3 expression during H2O2-induced apoptosis, suggesting that CaBP-28k blocks the up-regulation of apoptosis-related gene expression. siRNA knockdown of CaBP-28k resulted in an elevation of H2O2-induced cell death and an increase in Bax, p53 and caspase 3, providing additional evidence that induction of the CaBP-28k gene might be associated with survival signaling during H2O2-mediated cell death. Overall, these results suggest that CaBP-28k expression is inversely correlated with pro-apoptotic gene expression in human endometrial Ishikawa cells.