Reduced Levels of ATP Synthase Subunit ATP5F1A Correlate with Earlier-Onset Prostate Cancer.

René G Feichtinger,Georg Schäfer,Barbara Kofler,Helmut Klocker,Christof Seifarth,Johannes A Mayr

doi:10.1155/2018/1347174

René G Feichtinger, Georg Schäfer + Show 4 more

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https://doi.org/10.1155/2018/1347174

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Abstract

Switching of cellular energy production from oxidative phosphorylation (OXPHOS) to aerobic glycolysis occurs in many types of tumors. However, the significance of energy metabolism for the development of prostate carcinoma is poorly understood. We investigated the expression of OXPHOS complexes in 94 human prostate carcinomas and paired benign tissue using immunohistochemistry. Overall mitochondrial mass was upregulated in carcinomas compared to benign prostate tissue in all Gleason grades. A significant direct correlation between the expression of OXPHOS complexes I, II, and V and the Gleason score was observed. However, 17% of prostate carcinomas and 18% of benign prostate tissues showed isolated or combined deficiency of OXPHOS complexes (one deficiency in 12% of the tumors, combined deficiencies in 5%). Complex I was absent in 9% of the samples, with only parts of the tumor affected. ATP5F1A, a complex V protein, was the most frequently affected subunit, in 10% of tumors and 11% of benign prostate tissues (but not both tissues in any single patient). A possible role of complex V in prostate cancer development is suggested by the significant positive correlation of ATP5F1A levels with earlier-onset prostate cancer (age at diagnosis and at prostatectomy) and free PSA percentage. The relatively high percentage (17%) of prostate carcinomas with regional foci of partial OXPHOS complex deficiencies could have important therapeutic implications.

Highlights

Metabolism, especially energy metabolism, is a hot topic in tumor biology
To elucidate if prostate carcinomas and adjacent benign prostate tissue differ in terms of protein expression of the oxidative phosphorylation (OXPHOS) complexes and mitochondrial biogenesis, we immunohistochemically stained prostate carcinomas (n~94) and corresponding benign prostate tissue (n~89)
We stained for VDAC1, a protein of the outer mitochondrial membrane, as an indicator of mitochondrial mass and mitochondrial biogenesis

Summary

Introduction

Metabolism, especially energy metabolism, is a hot topic in tumor biology. A single tumor entity can be divided into subgroups, where one group shows high levels of oxidative phosphorylation (OXPHOS) and the other is deficient in one or more OXPHOS complexes, as found in melanomas [1]. Some tumor entities are very homogeneous in their OXPHOS signature; for example, neuroblastomas and renal cell carcinomas both show significant reductions of all OXPHOS complexes. The mode of downregulation of OXPHOS can vary (loss of mitochondria, loss of all complexes, isolated and combined deficiencies), most tumors have one feature in common—disruption of respiratory chain complex I [1,2,3,4,5,6,7,8,9,10,11,12,13]

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