Department of Dermatology, Field of Sensory Organology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
J Dermatol Sci. 2012 Oct;68(1):19-24. doi: 10.1016/j.jdermsci.2012.07.005. Epub 2012 Aug 2.
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.
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.
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.
We propose p53R2 as a therapeutic target to enhance the effectiveness of chemotherapy in patients with p53R2-positive melanoma.
黑色素瘤是一种侵袭性的、对化疗耐药的皮肤癌，其特征是快速转移和预后不良，需要开发具有改善疗效的创新疗法。p53R2 基因编码核糖核苷酸还原酶小亚基 2 同源物，可被多种应激信号诱导，包括激活 p53 的 DNA 损伤剂。p53R2 基因产物增加细胞核中的脱氧核苷酸三磷酸池；这有利于 DNA 修复和合成。
我们研究了黑色素瘤中 p53R2 的表达，并评估了 p53R2 是否参与黑色素瘤细胞的生长和增殖。方法我们检查了 p53R2 在黑色素瘤中的临床病理意义。为了研究 p53R2 在黑色素瘤中的作用，我们使用了表达 p53R2 的 KHm5 和 KHm6 黑色素瘤细胞和 p53R2 靶向小干扰 (si) RNA。
p53R2 的表达在 78 例患者中的 56 例（71.8%）中通过免疫组织化学法检测到。p53R2 的表达与浸润深度和肿瘤分期显著相关。p53R2 靶向 siRNA 成功敲低了 p53R2，并显著抑制了 KHm5 和 6 细胞的生长。此外，在存在 p53R2 靶向 siRNA 和尼莫司汀（ACNU）的情况下，KHm5 和 6 细胞的生长抑制程度大于单独使用 ACNU，表明 p53R2 沉默增强了 KHm5 和 6 细胞对 ACNU 的化疗敏感性。
我们提出 p53R2 作为一种治疗靶点，以增强 p53R2 阳性黑色素瘤患者化疗的效果。
