title: Autophagy-associated proteins BAG3 and p62 in testicular cancer.
abstract: Testicular germ cell tumors (TGCT) represent the most common malignant tumor group in the age group of 20 to 40-years old men. The potentially curable effect of cytotoxic therapy in TGCT is mediated mainly by the induction of apoptosis. Autophagy has been discussed as an alternative mechanism of cell death but also of treatment resistance in various types of tumors. However, in TGCT the expression and role of core autophagy-associated factors is hitherto unknown. We designed the study in order to evaluate the potential role of autophagy-associated factors in the development and progression of testicular cancers. Eighty-four patients were assessed for autophagy (BAG3, p62) and apoptosis (cleaved caspase 3) markers using immunohistochemistry (IHC) on tissue micro- arrays. In addition, western blot analyses of frozen tissue of seminoma and non-seminoma were performed. Our findings show that BAG3 was significantly upregulated in seminoma as compared to non-seminoma but not to normal testicular tissue. No significant difference of p62 expression was detected between neoplastic and normal tissue or between seminoma and non-seminoma. BAG3 and p62 showed distinct loco‑regional expression patterns in normal and neoplastic human testicular tissues. In contrast to the autophagic markers, apoptosis rate was significantly higher in testicular tumors as compared to normal testicular tissue, but not between different TGCT subtypes. The present study, for the first time, examined the expression of central autophagy proteins BAG3 and p62 in testicular cancer. Our findings imply that in general apoptosis but not autophagy induction differs between normal and neoplastic testis tissue.
authors.affiliation: Department of Urology, Goethe University Frankfurt/Main, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University Frankfurt/Main, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Jennewein
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University Frankfurt/Main, Germany.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.affiliation: Experimental Neurosurgery, Goethe University of Frankfurt/Main, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Antonietti
authors.affiliation: Department of Urology, Goethe University Frankfurt/Main, Germany.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Blaheta
authors.affiliation: German Cancer Consortium (DKTK) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Kvasnicka
authors.affiliation: German Cancer Consortium (DKTK) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors.forename: Donat
authors.initials: D
authors.lastname: Kögel
authors.affiliation: Department of Urology, Goethe University Frankfurt/Main, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University Frankfurt/Main, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Department of Urology, Goethe University Frankfurt/Main, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Mani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D018239:Seminoma / Q000235:genetics* / Q000473:pathology; D000071456:Sequestosome-1 Protein; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D013737:Testis / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein