Induction of thyroid gene expression and radioiodine uptake in melanoma cells: novel therapeutic implications.
Induction of thyroid gene expression and radioiodine uptake in melanoma cells: novel therapeutic implications.
复制标题
DOI：
10.1371/journal.pone.0006200
复制
发表时间：
2009-07-10
期刊：
影响因子：
3.7
通讯作者：
Xing M
中科院分区：
文献类型：
--
作者：
Hou P;Liu D;Ji M;Liu Z;Engles JM;Wahl RL;Xing M
MAP激酶和PI 3 K/Akt途径在黑色素瘤的发病机制中发挥重要作用。我们进行了本研究，以测试这一假设，靶向两个途径，以有效地诱导细胞抑制伴随甲状腺碘处理基因表达的辅助放射性碘消融可能是一种新的有效的治疗策略黑色素瘤。我们使用特定的shRNA方法和抑制剂来单独或双重抑制MAP激酶和PI 3 K/Akt通路，并检查了对黑色素瘤细胞的各种分子和细胞反应的影响，这些细胞在两种通路中具有激活的遗传改变。MAP激酶和PI 3 K/Akt通路的抑制显示出有效的抗黑色素瘤细胞作用，包括抑制细胞增殖、转化和侵袭，诱导G 0/G1细胞周期停滞，并且当这两条通路被双重抑制时，细胞凋亡。值得注意的是，抑制这两种途径，特别是同时抑制它们，也诱导了甲状腺中正常表达的基因的表达，如钠/碘同向转运体和促甲状腺激素受体的基因。因此，黑色素瘤细胞被赋予摄取放射性碘的能力。我们的结论是，双重靶向MAP激酶和PI 3 K/Akt通路的有效细胞抑制加上诱导甲状腺基因表达的辅助放射性碘消融治疗可能被证明是一种新的和有效的治疗策略黑色素瘤。
Both the MAP kinase and PI3K/Akt pathways play an important role in the pathogenesis of melanoma. We conducted the present study to test the hypothesis that targeting the two pathways to potently induce cell inhibition accompanied with thyroid iodide-handling gene expression for adjunct radioiodine ablation could be a novel effective therapeutic strategy for melanoma. We used specific shRNA approaches and inhibitors to individually or dually suppress the MAP kinase and PI3K/Akt pathways and examined the effects on a variety of molecular and cellular responses of melanoma cells that harbored activating genetic alterations in the two pathways. Suppression of the MAP kinase and PI3K/Akt pathways showed potent anti-melanoma cell effects, including the inhibition of cell proliferation, transformation and invasion, induction of G0/G1 cell cycle arrest and, when the two pathways were dually suppressed, cell apoptosis. Remarkably, suppression of the two pathways, particularly simultaneous suppression of them, also induced expression of genes that are normally expressed in the thyroid gland, such as the genes for sodium/iodide symporter and thyroid-stimulating hormone receptor. Melanoma cells were consequently conferred the ability to take up radioiodide. We conclude that dually targeting the MAP kinase and PI3K/Akt pathways for potent cell inhibition coupled with induction of thyroid gene expression for adjunct radioiodine ablation therapy may prove to be a novel and effective therapeutic strategy for melanoma.
登录
查看更多内容
影响因子：
5.8
作者：
Liu, Dingxie;Liu, Zhi;Xing, Mingzhao
通讯作者：
Xing, Mingzhao
影响因子：
8
作者：
Giordano, TJ;Kuick, R;Nikiforov, YE
通讯作者：
Nikiforov, YE
影响因子：
8
作者：
Cass, LA;Meinkoth, JL
通讯作者：
Meinkoth, JL
DOI：
10.1007/1-84628-013-3_1
发表时间：
2006-01-01
期刊：
PRACTICAL MANAGEMENT OF THYROID CANCER: MULTIDISCIPLINARY APPROACH
影响因子：
--
作者：
Mazzaferri, Ernest L.
通讯作者：
Mazzaferri, Ernest L.
影响因子：
10.3
作者：
Meier, F.;Busch, S.;Schittek, B.
通讯作者：
Schittek, B.