The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression
The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression
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DOI：
10.7150/jca.13207
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发表时间：
2016-01-01
影响因子：
3.9
通讯作者：
Kang, Dongchon
中科院分区：
文献类型：
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作者：
Amamoto, Rie;Uchiumi, Takeshi;Kang, Dongchon
背景：线粒体在细胞信号传导事件、细胞间通讯、衰老、细胞增殖和凋亡中发挥着至关重要的作用，线粒体损伤已被证明可以加速或调节癌症进展。普遍存在的线粒体肌酸激酶 (uMtCK) 主要位于线粒体的膜间隙中，催化三磷酸腺苷 (ATP) 和磷酸肌酸之间高能磷酸盐的可逆交换。然而，对其在人类前列腺癌进展中的表达和功能知之甚少。方法：我们通过免疫组织化学方法研究了uMtCK在148个前列腺癌组织和匹配的正常组织中的表达。使用蛋白质印迹和免疫荧光检查前列腺癌细胞系中uMtCK和糖酵解标志物己糖激酶II的表达和定位。结果：与正常前列腺或低级别癌相比，高格里森级别癌中MtCK的表达显着降低。 Western blot进一步显示uMtCK在LNCaP和22Rv1细胞系以及正常前列腺细胞系RWPE-1中高表达。然而，uMtCK 表达在 PC3 和 DU145 细胞系中几乎不存在，分别与 p53 表达缺失或突变相关。相反，己糖激酶 II 在 PC3 细胞中过度表达。此外，在低 uMtCK 表达的细胞系中，糖酵解 ATP 产量增加，而线粒体 ATP 产量减少。结论：这些数据表明，随着前列腺癌的进展，uMtCK 下调，与 ATP 使用的代谢转换相关。
Background: Mitochondria play crucial roles in cell signaling events, interorganellar communication, aging, cell proliferation and apoptosis, and mitochondrial impairment has been shown to accelerate or modulate cancer progression. Ubiquitous mitochondrial creatine kinase (uMtCK) is predominantly localized in the intermembrane space of mitochondria and catalyzes the reversible exchange of high-energy phosphate between adenosine tri-phosphate (ATP) and phosphocreatine. However, little is known about its expression and function in human prostate cancer progression.Method: We investigated the expression of uMtCK in 148 prostate carcinoma tissues and matched normal tissue by immunohistochemistry. The expression and localization of uMtCK and hexokinase II, a marker of glycolysis, were examined in prostate carcinoma cell lines using western blot and immunofluorescence.Results: MtCK expression was significantly lower in high Gleason grade carcinoma compared with normal prostate or low grade carcinoma. Western blot further revealed that uMtCK was highly expressed in LNCaP and 22Rv1 cell lines, as well as in the normal prostate cell line RWPE-1. However, uMtCK expression was almost absent in PC3 and DU145 cell lines, in correlation with absent or mutant p53 expression, respectively. In contrast, hexokinase II was overexpressed in PC3 cells. Moreover, in the low uMtCK expressing cell lines, glycolytic ATP production was increased, whereas mitochondrial ATP production was decreased.Conclusions: These data suggest that uMtCK is downregulated as prostate cancer progresses in correlation with a metabolic switch in ATP usage.