Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
Mol Cell Endocrinol. 2010 May 14;320(1-2):128-35. doi: 10.1016/j.mce.2010.02.004. Epub 2010 Feb 6.
Thyroid cancer is the most common endocrine malignancy and exhibits the full range of malignant behaviors from the relatively indolent occult differentiated thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer. Iodine is a well known key element in thyroid normal function maintenance and thyroid cancer development. However, the effects induced by iodine and the molecular mechanisms involved remain poorly understood in thyroid cancer. We investigated the apoptotic effect of iodine on three different subtypes of thyroid cancer cells. We observed that apoptosis induced by iodine was mitochondrial-mediated. Iodine treatment decreased the level of mutant p53 including the R273H mutant that possesses anti-apoptotic features, but increased the p21 level. Surprisingly, high doses of iodine promoted instead of suppressed the expression of anti-apoptotic protein Bcl-xL expression. Moreover, iodine transiently activated the subfamily members of mitogen activated protein kinases (MAPKs) (ERK1/2, p38 and JNK1/2) which contribute to modulate p53, p21 and Bcl-xL expression. The further results showed the three subfamily members of MAPKs all worked as anti-apoptotic factors. Collectively, iodine-induced apoptotic pathway is involved in the activation of MAPKs-related p21, Bcl-xL and mutant p53 regulation. The findings provide solid molecular evidence to explain the potential pathway for iodine to influence thyroid cancer development. It may also reveal some novel molecular targets for the treatment of thyroid cancer.
甲状腺癌是最常见的内分泌恶性肿瘤，其恶性行为表现多样，从相对惰性的隐匿性分化型甲状腺癌到均匀侵袭性和致命性的间变性甲状腺癌。碘是甲状腺正常功能维持和甲状腺癌发展的重要元素。然而，碘的作用及其相关的分子机制在甲状腺癌中仍知之甚少。我们研究了碘对三种不同亚型甲状腺癌细胞的凋亡作用。我们观察到碘诱导的凋亡是线粒体介导的。碘处理降低了包括具有抗凋亡特征的 R273H 突变体在内的突变型 p53 的水平，但增加了 p21 的水平。令人惊讶的是，高剂量的碘反而促进了而非抑制了抗凋亡蛋白 Bcl-xL 的表达。此外，碘瞬时激活了丝裂原激活蛋白激酶（MAPKs）的亚家族成员（ERK1/2、p38 和 JNK1/2），这些成员有助于调节 p53、p21 和 Bcl-xL 的表达。进一步的结果表明，MAPKs 的三个亚家族成员都作为抗凋亡因子发挥作用。综上所述，碘诱导的凋亡途径涉及 MAPKs 相关的 p21、Bcl-xL 和突变型 p53 调节的激活。这些发现为碘影响甲状腺癌发展的潜在途径提供了确凿的分子证据。它也可能为甲状腺癌的治疗揭示一些新的分子靶点。
