The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways
The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways
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DOI：
10.1111/j.1464-410x.2005.05527.x
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发表时间：
2005-06-01
影响因子：
4.5
通讯作者：
Bartlett, JMS
中科院分区：
文献类型：
--
作者：
Edwards, J;Bartlett, JMS
前列腺癌是西方世界男性癌症相关死亡的第二大原因。在过去的50年里，前列腺癌的治疗一直依赖于雄激素剥夺疗法。最初的反应率很高（70-80%），但几乎所有患者都发生雄激素逃逸，随后在1-2年内死亡。与乳腺癌不同，替代方法（化疗和放疗）不会增加生存时间。因此，前列腺癌的高死亡率与雄激素逃逸和缺乏替代疗法密切相关。AR突变和扩增不能解释雄激素逃逸的所有情况，AR的翻译后修饰已成为另一种理论。然而，最近已经提出，AR共激活剂例如SRC-1或绕过AR的途径（Ras/MAP激酶或PI 3 K/Akt）可以独立于AR刺激前列腺癌进展。这篇综述将集中在AR coactivators可能会采取行动，以增加AR的反式激活在次优的DHT浓度，以及如何信号转导途径可能会促进雄激素逃逸通过激活转录因子，如AP-1，c-Myc和Myb，诱导细胞增殖或抑制凋亡。
Prostate cancer is the second leading cause of cancer related deaths in men from the western world. Treatment of prostate cancer has relied on androgen deprivation therapy for the past 50 years. Response rates are initially high (70-80%), however almost all patients develop androgen escape and subsequently die within 1-2 years. Unlike breast cancer, alternative approaches (chemotherapy and radiotherapy) do not increase survival time. The high rate of prostate cancer mortality is therefore strongly linked to both development of androgen escape and the lack of alternate therapies. AR mutations and amplifications can not explain all cases of androgen escape and post-translational modification of the AR has become an alternative theory. However recently it has been suggested that AR co-activators e.g. SRC-1 or pathways the bypass the AR (Ras/MAP kinase or PI3K/Akt) may stimulated prostate cancer progression independent of the AR. This review will focus on how AR coactivators may act to increase AR transactivation during sub-optimal DHT concentrations and also how signal transduction pathways may promote androgen escape via activation of transcription factors, e.g. AP-1, c-Myc and Myb, that induce cell proliferation or inhibit apoptosis.