RGD Reference Report - Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell Carcinoma. - Rat Genome Database

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Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell Carcinoma.

Authors: Brüggemann, Maria  Gromes, Arabella  Poss, Mirjam  Schmidt, Doris  Klümper, Niklas  Tolkach, Yuri  Dietrich, Dimo  Kristiansen, Glen  Müller, Stefan C  Ellinger, Jörg 
Citation: Brüggemann M, etal., Transl Oncol. 2017 Aug;10(4):661-668. doi: 10.1016/j.tranon.2017.06.002. Epub 2017 Jun 30.
RGD ID: 14696810
Pubmed: PMID:28672194   (View Abstract at PubMed)
PMCID: PMC5496479   (View Article at PubMed Central)
DOI: DOI:10.1016/j.tranon.2017.06.002   (Journal Full-text)

Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n=18 and normal renal tissue n=10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n=74; normal renal tissue n=36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Atp5mc2  (ATP synthase membrane subunit c locus 2)
Atp5pb  (ATP synthase peripheral stalk-membrane subunit b)
Atp5po  (ATP synthase peripheral stalk subunit OSCP)

Genes (Mus musculus)
Atp5mc2  (ATP synthase membrane subunit c locus 2)
Atp5pb  (ATP synthase peripheral stalk-membrane subunit b)
Atp5po  (ATP synthase peripheral stalk subunit OSCP)

Genes (Homo sapiens)
ATP5MC2  (ATP synthase membrane subunit c locus 2)
ATP5PB  (ATP synthase peripheral stalk-membrane subunit b)
ATP5PO  (ATP synthase peripheral stalk subunit OSCP)


Additional Information