Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis
Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis
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DOI：
10.1006/taap.1999.8907
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发表时间：
2000-05-01
影响因子：
3.8
通讯作者：
Waalkes, MP
中科院分区：
文献类型：
--
作者：
Achanzar, WE;Achanzar, KB;Waalkes, MP
镉是一种可疑的人类前列腺致癌物质，可诱导大鼠前列腺肿瘤和增生性病变。镉的致癌机制尚不清楚，但其不良的致突变性指向表观遗传机制。在这里，我们研究了镉对前列腺上皮细胞的生长调节基因的影响，使用人前列腺上皮细胞系RWPE-1，这是永生化的，但不转化，是雄激素反应。10 μ M镉处理导致c-myc和p53 mRNA水平的瞬时增加，2小时后分别达到对照的2倍和1.4倍。相反，c-jun mRNA水平在镉暴露2、4和6 h后增加>3倍，24 h后增加20倍，DNA合成在镉暴露24 h后减少。进一步的研究表明，镉暴露48小时后，细胞凋亡显着增加。然而，大约有358个细胞仍然存活，并且看起来正常，这表明这个亚群对镉的抵抗力更强。此外，这些耐药细胞的金属硫蛋白比未处理的对照细胞多2.5倍。这表明，镉可以在体内选择有肿瘤缺陷的细胞，从而增加肿瘤形成的可能性。这项工作是第一次描述镉影响癌基因表达的人体细胞模型的一个潜在的体内镉致癌作用的靶位点。(C)北京大学出版社.
Cadmium is a suspected human prostatic carcinogen shown to induce prostatic tumors and proliferative lesions in rats. The carcinogenic mechanism of cadmium is unknown, but its poor mutagenicity points toward an epigenetic mechanism. Here we studied the effect of cadmium on genes involved in growth regulation of prostate epithelial cell using the human prostate epithelial cell line RWPE-1, which is immortalized but not transformed and is androgen-responsive. Treatment with 10 mu M cadmium resulted in transient increases in c-myc and p53 mRNA levels that peaked at 2-fold and 1.4-fold, respectively, compared to control after 2 h. In contrast, c-jun mRNA levels were increased >3-fold after 2, 4, and 6 h and 20-fold after 24 h, DNA synthesis decreased after 24 h of cadmium exposure. Further study revealed a significant increase in apoptosis after 48 h of cadmium exposure. However, approximately 358 of the cells were still viable and appeared normal, indicating this subpopulation was more resistant to cadmium. Furthermore, these resistant cells had 2.5-fold more metallothionein than untreated control cells. This suggests that cadmium could act to select for apoptotic-defective cells in vivo, thereby increasing the likelihood of tumor formation. This work represents the first description of cadmium affecting oncogene expression in a human cell model of a potential in vivo target site of cadmium carcinogenesis. (C) 2000 Academic Press.