前列腺癌相关基因PC-1(Prostate and colon gene 1)是属于癌基因D52家族成员, 具有促进前列腺癌细胞雄激素非依赖性生长的功能。为了研究PC-1发挥这种生物功能的分子机制, 文章在PC-1高表达的LNCaP-pc-1及对照LNCaP-zero细胞中, 利用RT-PCR和Western blotting等方法检测c-myc基因表达; 提取两细胞胞质和胞核蛋白, 利用Western blotting分析c-myc上游调节蛋白β-catenin变化; 利用c-Myc蛋白抑制剂10058-F4作用前列腺癌细胞C4-2, Western blotting检测PC-1蛋白表达变化。发现PC-1促进c-myc基因表达, 并促进β-catenin入核; c-Myc蛋白抑制剂10058-F4可抑制PC-1的表达。结果表明: PC-1在前列腺癌中促进c-myc基因的表达, 并且这种促进作用可能是通过Wnt/β-catenin信号通路实现的。同时, PC-1与c-Myc蛋白间可相互促进, 进一步促进前列腺癌细胞雄激素非依赖性生长。
PC-1(Prostate and colon gene 1) gene belongs to TPD52 (Tumor Protein D52) gene family. The expression of PC-1 is found to promote androgen-independent progression. This study was conducted to assess the mechnism of promotion of androgen-independent progression in PC-1 gene. The c-myc gene expression was tested by RT-PCR and Western blotting analyses in the LNCaP-pc-1 and LNCaP-zero cell line. After separation of cytoplasm and nulear proteins of the LNCaP-pc-1 and LNCaP-zero cell line, the β-catenin protein was detected by Western blotting. C4-2 cell line was used to examine the effects of 10058-F4 on the PC-1 gene expression. The results of RT-PCR and Western blotting indicated that PC-1 enhanced c-myc gene expression in prostate cancer cells, PC-1 was also found to enhance β-catenin expression in nuclear. Furthermore, a small-molecule c-Myc inhibitor, 10058-F4 represses PC-1 gene expression in C4-2 cell line. Our findings suggest that PC-1 enhances c-myc gene expression in prostate cancer cells through the Wnt/β-catenin pathway. Meanwhile, c-myc plays a feed-forward role in enhancing PC-1 driven c-myc gene expression, and promotes prostate an-drogen-independent progression.
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