The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression
| Autor: | Masaki Shiota, Dongchon Kang, Keisuke Monji, Rie Amamoto, Mikako Yagi, Takeshi Uchiumi, Akira Yokomizo, Yoshinao Oda, Seiji Naito, YooHyun Song |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Biology Mitochondrion Phosphocreatine 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine DU145 LNCaP medicine Glycolysis mtCK Cell growth medicine.disease ATP mitochondria 030104 developmental biology Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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