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Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer
Author(s) -
Herrmann Paul C.,
Gillespie John W.,
Charboneau Lu,
Bichsel Verena E.,
Paweletz Cloud P.,
Calvert Valerie S.,
Kohn Elise C.,
EmmertBuck Michael R.,
Liotta Lance A.,
Petricoin Emanuel F.
Publication year - 2003
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200300461
Subject(s) - cytochrome c oxidase , biology , microbiology and biotechnology , protein subunit , mitochondrion , laser capture microdissection , carcinogenesis , cytochrome c , biochemistry , gene , gene expression
Laser capture microdissection was combined with reverse phase protein lysate arrays to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I‐III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV–VIII) are synthesized from cellular nuclear DNA. A significant ( P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and VIc compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array‐based observations were corroborated with immunohistochemistry, and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome.