High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays.
High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays.
复制标题
DOI：
10.1371/journal.pone.0022096
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Becker JC
中科院分区：
文献类型：
--
作者：
Houben R;Hesbacher S;Schmid CP;Kauczok CS;Flohr U;Haferkamp S;Müller CS;Schrama D;Wischhusen J;Becker JC
控制细胞周期进程、细胞凋亡和衰老的P53通路失活被认为发生在几乎所有人类肿瘤中，而P53是人类癌症中最常见的突变蛋白。然而，P53在黑色素瘤中的突变状态仍然存在争议；为了澄清这一概念，我们分析了迄今为止报告的最大系列黑色素瘤样本。对180多个黑色素瘤标本的免疫组织化学分析表明，绝大多数病例都有高水平的P53表达。然而，随后对p53外显子5-8进行测序后，只有一例发现了突变的存在。然而，通过两种不同的P53报告结构，我们发现在10个黑色素瘤细胞系中有6个野生型P53转录失活；另外4个P53野生型黑色素瘤细胞株表现出P53报告基因的活性，这可以被P53的shRNA敲除而被阻断。在表达高水平野生型P53的黑色素瘤中，这种肿瘤抑制因子经常在转录水平失活。
Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.
登录
查看更多内容
影响因子：
6.5
作者：
Haferkamp, Sebastian;Scurr, Lyndee L.;Rizos, Helen
通讯作者：
Rizos, Helen
影响因子：
64.5
作者：
Kruse JP;Gu W
通讯作者：
Gu W
影响因子：
6.4
作者：
CASTRESANA, JS;RUBIO, MP;BARNHILL, RL
通讯作者：
BARNHILL, RL
影响因子：
8
作者：
Homer, C;Knight, DA;Braithwaite, AW
通讯作者：
Braithwaite, AW
影响因子：
30.8
作者：
Bergamaschi, D;Samuels, Y;Lu, X
通讯作者：
Lu, X