Upregulation of HMG1 leads to melanoma inhibitory activity expression in malignant melanoma cells and contributes to their malignancy phenotype
Upregulation of HMG1 leads to melanoma inhibitory activity expression in malignant melanoma cells and contributes to their malignancy phenotype
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DOI：
10.1128/mcb.23.8.2991-2998.2003
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发表时间：
2003-04-01
影响因子：
5.3
通讯作者：
Bosserhoff, AK
中科院分区：
文献类型：
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作者：
Poser, I;Golob, M;Bosserhoff, AK
黑素细胞向黑色素瘤细胞的恶性转化与黑色素瘤抑制活性（MIA）表达的激活密切平行。我们以前已经表明，MIA的上调发生在转录水平上，并涉及高度保守区（HCR）启动子元件。我们进一步观察到HCR元件与黑素瘤相关转录因子（MATF）相互作用，从而赋予强启动子激活。在这项研究中，我们确定的肽序列的MATF，并表明它是相同的转录因子HMG 1。HMG 1在恶性黑色素瘤细胞中上调，并通过低磷酸化进一步激活。在黑色素瘤细胞中稳定的反义HMG 1表达导致MIA启动子活性和蛋白表达的降低，表明HMG 1是MIA表达的有效调节剂。有趣的是，染色质免疫沉淀和电泳迁移率变化实验表明，HMG 1和NF-κ B家族成员p65都相互作用，并结合到HCR启动子元件。总之，我们的研究证明HMG 1和p65是MIA调节和黑色素瘤进展的重要因素。
Malignant transformation of melanocytes to melanoma cells closely parallels activation of melanoma inhibitory activity (MIA) expression. We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element. We further observed that the HCR element interacts with the melanoma-associated transcription factor (MATF) and thereby confers strong promoter activation. In this study we identify the peptide sequence of MATF and show that it is identical with the transcription factor HMG1. HMG1 was upregulated in malignant melanoma cells and further activated by hypophosphorylation. Stable antisense-HMG1 expression in melanoma cells led to the reduction of MIA promoter activity and protein expression, indicating that HMG1 is a potent regulator of MIA expression. Interestingly, chromatin immunoprecipitation and electrophoretic mobility shift experiments indicated that HMG1 and the NF-kappaB family member p65 both interact and bind to the HCR promoter element. In summary, our study proves HMG1 and p65 to be important factors in MIA regulation and melanoma progression.