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正常和恶性人黑素细胞中wt1肾母细胞瘤基因的表达。

Expression of the wt1 Wilms' tumor gene by normal and malignant human melanocytes.

作者信息

Rodeck U, Bossler A, Kari C, Humphreys C W, Györfi T, Maurer J, Thiel E, Menssen H D

机构信息

Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

出版信息

Int J Cancer. 1994 Oct 1;59(1):78-82. doi: 10.1002/ijc.2910590116.

Abstract

We report expression of the wt1 (Wilms' tumor) gene by cultured human melanoma cells. Using RNA polymerase chain reaction analysis, wt1 transcripts were detected in 7 of 9 melanoma cell lines but not in 5 normal melanocyte strains. In Northern blot analysis, steady-state wt1 mRNA levels were found in 2 of 4 melanoma lines but not in normal melanocytes. Sequence analysis of the wt1 cDNA expressed by melanoma cell line WM 902-B revealed the presence of 4 previously published splice variants but no evidence for mutations in the coding region. Previous work has shown that WT1 modulates transcription after binding to the early growth response (EGR)-1 sites present in the platelet-derived growth factor (PDGF)-A chain promoter; the PDGF-A chain gene is known to be expressed by various melanoma cell lines. Based on these findings, we studied the relationship of wt1 and PDGF-A chain gene expression in melanoma cell lines. Co-expression of the wt1 and the PDGF-A chain genes was observed in 2 melanoma cell lines with mutated p53 but not in 2 melanoma cell lines with wild-type p53; this result is consistent with a previous report showing that, in the context of absent or mutated p53, WT1 acts as a transcriptional activator, whereas in the presence of wild-type p53 it acts as a repressor.

摘要

我们报告了培养的人黑色素瘤细胞中wt1(威尔姆斯瘤)基因的表达情况。通过RNA聚合酶链反应分析,在9个黑色素瘤细胞系中的7个中检测到了wt1转录本,而在5个正常黑素细胞株中未检测到。在Northern印迹分析中,在4个黑色素瘤细胞系中的2个中发现了稳定状态的wt1 mRNA水平,而在正常黑素细胞中未发现。对黑色素瘤细胞系WM 902 - B表达的wt1 cDNA进行序列分析,发现存在4种先前发表的剪接变体,但没有证据表明编码区存在突变。先前的研究表明,WT1与血小板衍生生长因子(PDGF)-A链启动子中存在的早期生长反应(EGR)-1位点结合后可调节转录;已知PDGF - A链基因可由多种黑色素瘤细胞系表达。基于这些发现,我们研究了黑色素瘤细胞系中wt1与PDGF - A链基因表达的关系。在2个p53突变的黑色素瘤细胞系中观察到wt1和PDGF - A链基因的共表达,而在2个p53野生型的黑色素瘤细胞系中未观察到;这一结果与先前的一份报告一致,该报告表明,在p53缺失或突变的情况下,WT1作为转录激活因子起作用,而在野生型p53存在的情况下,它作为转录抑制因子起作用。

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