ICER reverses tumorigenesis of rat prostate tumor cells without affecting cell growth.
ICER reverses tumorigenesis of rat prostate tumor cells without affecting cell growth.
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ICER 可逆转大鼠前列腺肿瘤细胞的肿瘤发生而不影响细胞生长。
DOI：
10.1002/pros.10149
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Molina,CarlosA
中科院分区：
文献类型：
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作者：
Mémin,Elisabeth;Yehia,Ghassan;Razavi,Reza;Molina,CarlosA
背景：诱导型cAMP早期抑制因子(ICER)是cAMP抗增殖活性的重要介质，是肿瘤抑制基因产物。ICER是一种转录抑制因子，负向调节cAMP介导的基因表达。方法通过细胞计数、胸腺嘧啶核苷掺入、流式细胞仪、软琼脂集落形成和免疫缺陷裸小鼠生长等方法研究ICER稳定表达的AT6.3细胞克隆的增殖能力。CAMP可显著诱导AT6.3细胞ICER基因和蛋白的表达。ICER在AT6.3细胞中的强制表达不影响细胞生长、胸腺嘧啶核苷掺入或细胞周期。但这些携带ICER的AT6.3细胞不能在软琼脂中生长，也不能在裸鼠体内形成肿瘤。结论ICER特异性地影响前列腺癌细胞的成瘤性，而不影响其生长。因此，ICER表达的操纵可以用于雄激素不敏感的前列腺癌的治疗，而不会对细胞造成不良的毒性。前列腺癌53：225-231,2002。©2002 Wiley-Liss公司
BACKGROUNDInducible cAMP early repressor (ICER) is an important mediator of cAMP antiproliferative activity that acts as a putative tumor suppressor gene product. ICER is a transcriptional repressor that negatively regulates cAMP‐mediated gene expression. Here, we report the effect of ectopically increasing the expression of ICER on in vitro and in vivo proliferation of the highly metastatic and androgen‐insensitive AT6.3 rat prostate cells.METHODSThe proliferative potential of stable AT6.3 cell clones expressing ICER was studied by cell counts, thymidine incorporation, flow cytometry, colony formation in soft agar, and growth in immunodeficient nude mice.RESULTScAMP inhibits the growth of AT6.3 cells. ICER mRNA and protein levels were markedly induced by cAMP in AT6.3 cells. Forced expression of ICER in AT6.3 cells did not affect cell growth, thymidine incorporation, or the cell cycle. However, these ICER‐bearing AT6.3 cells were rendered unable to grow in soft agar or to form tumors in nude mice.CONCLUSIONThese results show that ICER specifically affects the tumorigenicity of prostate cancer cell without affecting their growth. Therefore, the manipulation of ICER expression could be used for the treatment of androgen‐insensitive prostate tumors without causing undesirable toxicity to the cells. Prostate 53: 225–231, 2002. © 2002 Wiley‐Liss, Inc.