title: The Expression of Ubiquitous Mitochondrial Creatine Kinase Is Downregulated as Prostate Cancer Progression.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: 1. Department of Clinical Chemistry and Laboratory Medicine ; 4. Department of Nutritional Sciences, Seinan Jo Gakuin University, Kitakyushu, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Amamoto
authors.affiliation: 1. Department of Clinical Chemistry and Laboratory Medicine.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.affiliation: 1. Department of Clinical Chemistry and Laboratory Medicine.
authors.forename: Mikako
authors.initials: M
authors.lastname: Yagi
authors.affiliation: 1. Department of Clinical Chemistry and Laboratory Medicine.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Monji
authors.affiliation: 2. Department of Anatomic Pathology ; 3. Department of Urology, Kyushu University, Fukuoka, Japan.
authors.forename: YooHyun
authors.initials: Y
authors.lastname: Song
authors.affiliation: 2. Department of Anatomic Pathology.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: 3. Department of Urology, Kyushu University, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.affiliation: 3. Department of Urology, Kyushu University, Fukuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: 3. Department of Urology, Kyushu University, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.affiliation: 1. Department of Clinical Chemistry and Laboratory Medicine.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
keywords: ATP; mitochondria; mtCK