• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biochemistry >STAT3 inhibition induces apoptosis in cancer cells independent of STAT1 or STAT2
【24h】

STAT3 inhibition induces apoptosis in cancer cells independent of STAT1 or STAT2

机译：STAT3抑制诱导癌细胞独立于STAT1或STAT2的凋亡

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Signal transducers and activators of transcription (STATs) were originally discovered as mediators of signal transduction. Persistent aberrant activation of STAT3 is part of the malignant phenotype of hormone-refractory prostate cancer and pancreatic cancer; this is thought to be mediated by homodimers of phosphorylated STAT3, which translocate to the nucleus. One consequence of persistently-activated STAT3 in malignant cells is that they depend upon it for survival. STAT3 is observed to heterodimerize with STAT1 and STAT2; however the contributions of STAT3:STAT1 and STAT3:STAT2 heterodimers to the survival of malignant cells have not been investigated in detail. Previously we reported that single-stranded oligonucleotides containing consensus STAT3 binding sequences (13410 and 13411) were more effective for inducing apoptosis in prostate cancer cells than antisense STAT3 oligonucleotides. Control oligonucleotides (scrambled sequences) had no effect. STAT3-inhibiting oligonucleotide 13410, but not scrambled-sequence oligonucleotides, induced apoptosis in pancreatic cancer cells as well. Here we report that 13410 and derivative olignucleotides induced apoptosis in STAT1-null and STAT2-null fibrosarcoma cell lines U3A and U6A, as well as in the parental fibrosarcoma cell line 2fTGH. The cell lines expressed constitutively-activated STAT3 and depended on its activity for survival. Forty-eight hr after transfection of 13410 or related oligonucleotides, significant apoptosis was observed in 2fTGH, U3A and U6A cells. Scrambled-sequence oligonucleotides had no effect on survival. These data indicate that neither STAT1 nor STAT2 play significant roles in the maintenance of these cells, and by extension that STAT3:STAT1 and STAT3:STAT2 heterodimers regulate a different set of genes from STAT3:STAT3 homodimers.
机译：最初发现信号转导子和转录激活子（STATs）作为信号转导的介质。 STAT3的持续异常激活是激素难治性前列腺癌和胰腺癌恶性表型的一部分。据认为，这是由磷酸化STAT3的同型二聚体介导的，所述同型二聚体易位至细胞核。 STAT3在恶性细胞中持续激活的结果之一是它们赖以生存。观察到STAT3与STAT1和STAT2异源二聚体;然而，尚未详细研究STAT3：STAT1和STAT3：STAT2异二聚体对恶性细胞存活的贡献。先前我们曾报道，含有共有STAT3结合序列（13410和13411）的单链寡核苷酸比反义STAT3寡核苷酸更有效地诱导前列腺癌细胞的凋亡。对照寡核苷酸（混乱的序列）没有作用。抑制STAT3的寡核苷酸13410，而非加扰序列的寡核苷酸，也诱导胰腺癌细胞的凋亡。在这里我们报告13410和衍生寡核苷酸诱导STAT1 null和STAT2 null的纤维肉瘤细胞系U3A和U6A，以及亲本纤维肉瘤细胞系2fTGH中的凋亡。细胞系表达组成性激活的STAT3，并取决于其存活活性。转染13410或相关寡核苷酸后48小时，在2fTGH，U3A和U6A细胞中观察到明显的凋亡。乱序寡核苷酸对存活没有影响。这些数据表明，STAT1和STAT2在维持这些细胞中均不发挥重要作用，并且据此进一步扩展了STAT3：STAT1和STAT3：STAT2异二聚体调控与STAT3：STAT3同二聚体不同的一组基因。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号