Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells
Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells
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DOI：
10.1046/j.1523-1747.2002.00111.x
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发表时间：
2002-10-01
影响因子：
6.5
通讯作者：
Borea, PA
中科院分区：
文献类型：
--
作者：
Merighi, S;Mirandola, P;Borea, PA
腺苷对细胞生长表现出相互矛盾的作用：它促进细胞增殖，但也可能诱导细胞凋亡并损害细胞存活。在人黑色素瘤细胞系A375上腺苷受体表达的药理学表征之后，我们选择A375作为我们的细胞模型来定义细胞外腺苷信号如何从每个受体传递。通过使用选择性腺苷受体激动剂或拮抗剂，我们发现A（2A）刺激降低了细胞活力和细胞克隆形成，而同时，它改善了细胞增殖。为了支持这一发现，我们证明了在中国仓鼠卵巢细胞克隆中稳定表达的A（2A）腺苷受体的刺激再现了在人黑素瘤细胞中观察到的有害作用。A（3）刺激抵消了A（2A）诱导的细胞死亡，但也降低了细胞增殖。此外，我们发现A（3）刺激确保细胞存活。我们证明腺苷通过A（3）受体激活触发存活信号，并通过A（2A）受体诱导涉及蛋白激酶C和促分裂原活化蛋白激酶的信号通路杀死细胞。
Adenosine displays contradictory effects on cell growth: it improves cell proliferation, but it may also induce apoptosis and impair cell survival. Following the pharmacologic characterization of adenosine receptor expression on the human melanoma cell line A375, we chose A375 as our cellular model to define how the extracellular adenosine signals are conveyed from each receptor. By using selective adenosine receptor agonists or antagonists, we found that A(2A) stimulation reduced cell viability and cell clone formation, whereas, at the same time, it improved cell proliferation. In support of this finding we demonstrated that the stimulation of A(2A) adenosine receptors stably expressed in Chinese hamster ovary cell clone reproduced deleterious effects observed in human melanoma cells. A(3) stimulation counteracted A(2A)-induced cell death but also reduced cell proliferation. Furthermore, we found that A(3) stimulation ensures cell survival. We demonstrated that adenosine triggers a survival signal via A(3) receptor activation and it kills the cell through A(2A) receptor inducing a signaling pathway that involves protein kinase C and mitogen-activated protein kinases.