Bioenergetic theory of prostate malignancy.
Normal and benign prostate hyperplasia (BPH) prostate is characterized by the presence of extraordinarily high levels of citrate. Presumably, this results from the inability of the prostate epithelial cells to oxidize citrate due to a limiting mitochondrial (m-) aconitase. In contrast, prostate carcinoma (CA) is not characterized by high citrate levels. Malignant prostate epithelial cells apparently undergo a metabolic transformation from citrate-producing to citrate-oxidizing cells. A consequence of citrate production in normal and BPH cells is an inefficient and low level of ATP production. It is proposed that the process of malignancy necessitates an energy production that cannot be provided by citrate-producing cells. Consequently, the transformation of prostate epithelial cells to citrate-oxidizing cells which increases the energy production capability is essential to the process of malignancy and metastasis. The metabolic transformation likely occurs as a premalignant or early malignant stage. This bioenergetic theory of prostate malignancy, if correct, will provide new approaches to the diagnosis and treatment of CA.
Costello
L C
LC
Department of Physiology, University of Maryland Dental School, Baltimore 21201.
Franklin
R B
RB
D000154:Aconitate Hydratase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002951:Citrates / Q000378:metabolism*; D019343:Citric Acid; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008954:Models, Biological; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D002951:Citrates; D019343:Citric Acid; D000255:Adenosine Triphosphate; D000154:Aconitate Hydratase