Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells.
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.
Mizumachi
Takatsugu
T
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Muskhelishvili
Levan
L
Naito
Akihiro
A
Furusawa
Jun
J
Fan
Chun-Yang
CY
Siegel
Eric R
ER
Kadlubar
Fred F
FF
Kumar
Udaya
U
Higuchi
Masahiro
M
D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D042282:Microdissection; D011467:Prostate / Q000166:cytology* / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm