Activation of the aryl hydrocarbon receptor by TCDD inhibits senescence: a tumor promoting event?
Activation of the aryl hydrocarbon receptor by TCDD inhibits senescence: a tumor promoting event?
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DOI：
10.1016/j.bcp.2008.11.022
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发表时间：
2009-02-15
影响因子：
5.8
通讯作者：
Swanson, H. I.
中科院分区：
文献类型：
--
作者：
Ray, S.;Swanson, H. I.
关键词：
激动剂2,3,7,8四氯二苯并-对二恶英（TCDD）激活芳烃受体（AHR） 1可促进肝脏和皮肤肿瘤的形成。在肝脏中，而不是皮肤中，ahr介导的促进TCDD肿瘤活性的事件已经进行了一些详细的研究，并且被认为涉及细胞命运过程的扰动。然而，使用培养细胞进行的研究经常产生明显矛盾的结果，表明TCDD对细胞命运过程的影响可能依赖于细胞环境。我们和其他人已经表明，在原代培养的角质形成细胞中，TCDD增加融合后增殖和晚期分化。此外，我们在这些细胞中进行的研究表明，TCDD也可以抑制培养诱导的衰老。虽然衰老作为一种永久性的细胞周期停滞，正在成为一个由癌基因调节的重要过程，并被认为具有治疗重要性，但其在TCDD/AHR介导的肿瘤促进中的作用尚未得到充分考虑。本文的目的是主要关注衰老作为一个与皮肤肿瘤发生相关的细胞过程，并探讨TCDD抑制衰老可能是其在皮肤中发挥促肿瘤作用的重要机制。
Activation of the aryl hydrocarbon receptor (AHR) 1 by the agonist, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) has been shown to promote tumor formation in both liver and skin. In the liver, but not the skin, the AHR-mediated events that contribute to TCDD’s tumor promoting activities have been studied in some detail and are thought to involve perturbation of cell fate processes. However, studies performed using cultured cells have often resulted in apparent contradictory results indicating that the impact of TCDD on cell fate processes may be cell context dependent. We and others have shown that in primary cultured keratinocytes TCDD increases post-confluent proliferation and increases late differentiation. Further, our studies performed in these cells indicate that TCDD can also inhibit culture-induced senescence. While senescence, a permanent cell cycle arrest, is emerging as an important process regulated by oncogenes and considered to be of therapeutic importance, its role with respect to TCDD/AHR mediated tumor promotion has not been fully considered. The intent of this article is to focus primarily on senescence as a cell process relevant to skin tumorigenesis and explore the idea that the inhibition of senescence by TCDD could be an important mechanism by which it may exert its tumor promoting effects in the skin.
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影响因子：
64.5
作者：
KNUTSON, JC;POLAND, A
通讯作者：
POLAND, A
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
10.5
作者：
Dankort, David;Filenova, Elena;McMahon, Martin
通讯作者：
McMahon, Martin
影响因子：
64.8
作者：
Evan, GI;Vousden, KH
通讯作者：
Vousden, KH
影响因子：
14.5
作者：
Blagosklonny, MV
通讯作者：
Blagosklonny, MV