The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Nutr Cancer. 2011;63(5):778-89. doi: 10.1080/01635581.2011.563029. Epub 2011 Jun 1.
We have shown that, in contrast to selenomethionine (SeMet) or selenite, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) exert prostate cancer (PCa) inhibitory effect in preclinical models. Here we investigated the prostate proteome signatures of mice treated with each selenium (Se) form for hypothesis generation concerning their potential in vivo molecular targets and cancer risk modification. Nude mice bearing subcutaneous PC-3 xenografts were treated daily with each Se form (3 mg Se/kg) orally for 45 days. Five prostates were pooled from each group. Their proteomes were profiled by LC-MS/MS with iTRAQ labeling. Of the 1,088 proteins identified, 72 were significantly modulated by one or more Se forms. MSeA and MSeC each induced separate sets of tumor suppressor proteins and suppressed different onco-proteins. Proteins induced by selenite and shared with MSeC were related to energy metabolism (e.g., fatty-acid synthase), and those induced by SeMet included vimentin and heat-shock protein-70, favoring cancer growth. While proteome changes induced by MSeA were associated with PCa risk reduction, desirable risk-reducing signatures induced by MSeC were counterbalanced by risk-promoting patterns shared with selenite and SeMet. We propose that the balance of oncogenic vs. suppressor protein patterns in the prostate may impact the direction of PCa risk modification by a given selenium.
我们已经表明，与硒代蛋氨酸（SeMet）或亚硒酸盐相比，甲基硒酸（MSeA）和硒代蛋氨酸（MSeC）在临床前模型中发挥了前列腺癌（PCa）抑制作用。在这里，我们研究了用每种硒形式处理的小鼠的前列腺蛋白质组特征，以生成关于它们在体内潜在分子靶标和癌症风险修饰的假设。用皮下 PC-3 异种移植物接种的裸鼠每天用每种硒形式（3mg Se/kg）口服治疗 45 天。每组从 5 个前列腺中提取蛋白质组。用 LC-MS/MS 和 iTRAQ 标记对其进行蛋白质组学分析。在鉴定的 1088 种蛋白质中，有 72 种被一种或多种硒形式显著调节。MSeA 和 MSeC 各自诱导了不同的肿瘤抑制蛋白，并抑制了不同的癌蛋白。亚硒酸盐和 MSeC 共同诱导的蛋白质与能量代谢有关（如脂肪酸合酶），而 SeMet 诱导的蛋白质包括波形蛋白和热休克蛋白-70，有利于癌症生长。虽然 MSeA 诱导的蛋白质组变化与降低 PCa 风险有关，但 MSeC 诱导的理想降低风险特征与亚硒酸盐和 SeMet 共享的促进风险模式相平衡。我们提出，前列腺中致癌蛋白与抑制蛋白模式的平衡可能会影响特定硒对 PCa 风险修饰的方向。
