Stathmin is involved in S100A4-mediated regulation of cell cycle progression
Stathmin is involved in S100A4-mediated regulation of cell cycle progression
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DOI：
10.1023/a:1006778804532
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发表时间：
1999-01-01
影响因子：
4
通讯作者：
Sherbet, GV
中科院分区：
文献类型：
--
作者：
Cajone, F;Sherbet, GV
S100A4是一个与细胞增殖和癌症转移相关的基因。先前的研究表明，S100A4的过表达会使细胞进入细胞周期的s期，同时p53的检测也会增强。这导致假设S100A4可能通过隔离p53和废除其G(1)-S检查点控制来控制细胞周期进程。S100A4诱导进入s期的细胞成功通过G(2)-M检查点控制。这里我们发现S100A4也参与了这个检查点的调控。已知Stathmin与p53一起参与控制G(2)-M转变。我们提供的证据表明，S100A4和stastmin基因的表达在呈指数增长的HeLa细胞中上调。当高温和4-羟基壬烯醛（4-HNE）抑制细胞增殖时，它们平行下调。我们假设S100A4可能直接诱导安定素上调，使细胞进入有丝分裂。由于已知野生型p53下调镇静素的表达，我们进一步假设这也可能与s100a4介导的p53隔离有关。血红素加氧酶（HO-1）是一种应激反应蛋白，已被用于监测热疗、12- o -十四醇磷酸13-醋酸酯（TPA）和4-HNE的影响。所有这些处理都诱导了HO-1，在全血清恢复的情况下，在血清缺乏中生长的细胞也诱导了HO-1。无论S100A4表达状态如何，HO-1诱导均发生。HO-1基因对许多血管生成药物具有响应元件，并诱导肿瘤的显著新生血管。因此，我们认为S100A4可能不具有血管生成特性。
S100A4 is a cell proliferation- and cancer metastasis-related gene. Previous studies have shown that over-expression of S100A4 drives the cells into the S-phase of the cell cycle, with concomitant enhancement of p53 detection. This has led to the postulate that S100A4 could be controlling cell cycle progression by sequestering p53 and abrogating its G(1)-S checkpoint control. Cells induced by S100A4 to enter the S-phase do successfully negotiate the G(2)-M checkpoint control. Here we show that S100A4 is also involved in the regulation of control at this checkpoint. Stathmin is known to be associated, together with p53 in controlling G(2)-M transition. We present evidence that the expression of S100A4 and stathmin genes is up regulated in exponentially growing HeLa cells. They are down regulated in parallel when cell proliferation is inhibited by hyperthermia and 4-hydroxynonenal (4-HNE). We postulate that S100A4 might directly induce stathmin up regulation to enable cells to enter into mitosis. Since wild-type p53 is known to down regulate stathmin expression, we further postulate this might also involve S100A4-mediated sequestration of p53. The expression of heme oxygenase (HO-1), a stress-response protein, has been used to monitor effects of hyperthermia, 12-O-tetradecanoly phorbol 13-acetate (TPA) and 4-HNE. All these treatments induced HO-1 and also when cells growing in serum-deficiency were restored with full serum. HO-1 induction occurred irrespective of S100A4 expression status. HO-1 gene has responsive elements for many angiogenic agents and induces marked neovascularisation of tumours. We suggest therefore that S100A4 may not possess angiogenic properties.