p53R2 is a prognostic factor of melanoma and regulates proliferation and chemosensitivity of melanoma cells
p53R2 is a prognostic factor of melanoma and regulates proliferation and chemosensitivity of melanoma cells
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DOI：
10.1016/j.jdermsci.2012.07.005
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发表时间：
2012-10-01
影响因子：
4.6
通讯作者：
Kanekura, Takuro
中科院分区：
文献类型：
--
作者：
Matsushita, Shigeto;Ikeda, Ryuji;Kanekura, Takuro
黑色素瘤是一种侵袭性、耐药性皮肤癌，其特点是转移快，预后差，需要开发具有改善疗效的创新疗法。编码核糖核苷酸还原酶小亚基2同源物的p53 R2基因由几种应激信号诱导，包括激活p53的DNA损伤剂。目的探讨p53 R2在黑色素瘤中的表达及其与黑色素瘤细胞生长增殖的关系。为了研究p53 R2在黑色素瘤中的作用，我们使用了表达p53 R2的KHm5和KHm6黑色素瘤细胞，以及p53 R2靶向的小干扰RNA。p53 R2的表达与肿瘤浸润深度、临床分期密切相关。靶向p53 R2的siRNA成功地敲除了p53 R2，并显著抑制了KHm5和6细胞的生长。p53 R2基因沉默可增强KHm5和6细胞对ACNU的敏感性。结论p53 R2基因沉默可作为治疗靶点，提高p53 R2阳性黑色素瘤患者的化疗效果。(c)2012年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background The treatment of melanoma, an aggressive, chemo-resistant skin cancer characterized by rapid metastasis and a poor prognosis, requires the development of innovative therapies with improved efficacy. The p53R2 gene that encodes the ribonucleotide reductase small subunit 2 homologue is induced by several stress signals including DNA-damaging agents that activate p53. The p53R2 gene product increases the deoxynucleotide triphosphate pool in the nucleus; this facilitates DNA repair and synthesis.Objective We examined the expression of p53R2 in melanoma and evaluated whether p53R2 is involved in the growth and proliferation of melanoma cells.Methods We examined the clinicopathological significance of p53R2 in melanoma. To investigate the role of p53R2 in melanoma we used KHm5 and KHm6 melanoma cells that express p53R2, and p53R2-targeting small interfering (si) RNA.Results p53R2 expression was detected immunohistochemically in 56 of 78 patients (71.8%). The expression of p53R2 was significantly correlated with the depth of invasion and the tumor stage. p53R2-targeting siRNA successfully knocked down p53R2 and significantly inhibited the growth of KHm5 and 6 cells. Moreover, The degree of KHm5 and 6 cell growth inhibition was greater in the presence of both p53R2-targeting siRNA and nimustine (ACNU) than with ACNU alone, suggesting that p53R2 silencing enhanced the chemosensitivity of KHm5 and 6 cells to ACNU.Conclusions We propose p53R2 as a therapeutic target to enhance the effectiveness of chemotherapy in patients with p53R2-positive melanoma. (c) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.