PAX4 has the potential to function as a tumor suppressor in human melanoma
PAX4 has the potential to function as a tumor suppressor in human melanoma
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DOI：
10.3892/ijo_00000095
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发表时间：
2008-11-01
影响因子：
5.2
通讯作者：
Moriuchi, Tetsuya
中科院分区：
文献类型：
--
作者：
Hata, Shinya;Hamada, Jun-Ichi;Moriuchi, Tetsuya
我们推测，在成人体内发育调控基因的表达水平失调导致肿瘤的发展和恶性进展。PAX基因作为果蝇“配对”的人类正向同源基因被发现，编码转录因子，控制靶基因的表达，使其沿着发育程序进行。在本研究中，我们首先定量9 PAX基因在人色素痣组织，黑色素瘤组织和黑色素瘤细胞系的表达通过实时逆转录-PCR方法。结果，我们发现，与色素痣组织相比，PAX 4和PAX 9的表达水平在黑素瘤组织和细胞系中极低。然后，我们建立了过表达PAX 4的黑色素瘤细胞，并研究了PAX 4在细胞生长中的作用。PAX 4-过氧化抑制人黑素瘤C8161和MeWo细胞的体外细胞生长。BrdU摄取实验和流式细胞仪细胞周期分析表明PAX 4过表达抑制细胞增殖是由于DNA合成减少和细胞周期停滞在G 0/G1期。此外，用5-氮杂胞苷（DNA去甲基化剂）处理C8161和MeWo细胞，诱导PAX 4的表达，表明DNA甲基化抑制了人黑素瘤中PAX 4基因的表达。这些结果表明PAX 4作为一种有效的肿瘤抑制剂发挥作用。
We hypothesize that dysregulated expression levels of the developmental regulatory genes in the adult body result in tumor development and malignant progression. PAX genes discovered as human orthologous genes of Drosophila 'paired' encode transcription factors, which control the expression of target genes to go on along the program of development. In this study, we first quantified expression of 9 PAX genes in human nevus pigmentosus tissues, melanoma tissues and melanoma cell lines by the real-time reverse transcription-PCR method. As a result, we found that the expression levels of PAX4 and PAX9 were extremely low in melanoma tissues and cell lines compared to nevus pigmentosus tissues. We then established melanoma cells overexpressing PAX4 and examined roles of PAX4 in cell growth. PAX4-overex press ion reduced in vitro cell growth of human melanoma C8161 and MeWo cells. BrdU-uptake assay and cell cycle analysis by flow cytometry indicated that the retardation of cell proliferation by PAX4-overexpression was due to decreased DNA synthesis and cell cycle arrest at the G0/G1 phase. Furthermore, treatment of C8161 and MeWo cells with 5-azacytidine, a DNA demethylating agent, induced the expression of PAX4, suggesting that DNA methylation repressed the PAX4 gene expression in human melanoma. These results suggest that PAX4 functions as a potent tumor suppressor.