Scientific Publications by FDA Staff

Prostate 2008 Mar 1;68(4):408-17

Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells.

Mizumachi T, Muskhelishvili L, Naito A, Furusawa J, Fan CY, Siegel ER, Kadlubar FF, Kumar U, Higuchi M

BACKGROUND: Mitochondria are key organelles for apoptosis, and mitochondrial DNA (mtDNA) content can regulate cancer progression. Increases in mtDNA mutations and deletions have been reported in cancer; however, a detailed investigation of mtDNA content in cancer cells has not yet been conducted. METHODS: Quantitative real-time PCR and improved extraction method were established to investigate the mtDNA content in a single prostate cell. RESULTS: The heterogeneity of mtDNA content was demonstrated between the clones of prostate cancer cell line LNCaP and individual cells in each clone. To investigate whether large distributional variance of mtDNA content is associated with cancer initiation and/or progression, we first compared PZ-HPV-7, an HPV-transformed normal prostate epithelial cell line, with CA-HPV-10, transformed from prostate cancer cells derived from the same donor. We found an enhanced distributional variance of mtDNA content in CA-HPV-10. Then, we investigated mtDNA content in individual cells in laser microdisssected cancer and adjacent normal cells from prostate cancer tissue specimens using quantitative real-time PCR method. Results showed that the mtDNA content per cell follows a higher skewed distribution in cancer cells as compared in normal cells. We also observed that mtDNA content was increased in seven of nine (78%) of prostate cancers compared to normal prostate tissue. CONCLUSIONS: These results indicate that prostate carcinogenesis may involve dysregulation of mtDNA content.