title: Testis cancer cells have a genetic determination for a high sensitivity to apoptosis inducing stimuli.
abstract: OBJECTIVE
  The effect of cytotoxic therapy in testicular tumors (TGCT) has been shown to be mediated mainly by the induction of apoptosis. So far, it is not known which genes play a role for this inherent sensitivity to apoptosis inducing drugs. The aim of this study was to investigate the differential gene expression of apoptosis regulating genes in testicular tumors and in normal testis tissue using a quantitative method. As a premature S-phase entry was shown to induce apoptosis, genes controlling the G1/S-phase checkpoint were also investigated.
  
  
  METHODS
  Gene expression levels of a representative subset of 19 genes involved in apoptosis and cell cycle control were investigated in vivo in 19 TGCTs using real-time quantitative PCR. Measurements were performed in tumor tissues of both tumor entities, seminomatous and non-seminomatous tumors (SGCT and NSGCT), and in corresponding biopsies from the unaffected site of the resected testis.
  
  
  RESULTS
  There was an up-regulation of genes that play a role in facilitating apoptosis, such as FasL, TRAIL, and Bax in both tumor entities. Genes inhibiting apoptosis, such as Bcl-2 were predominantly down-regulated. Regarding cell cycle regulators, a gene expression profile was found that corresponds to a premature S phase entry and subsequent apoptosis induction.
  
  
  CONCLUSIONS
  This study for the first time identified in vivo a panel of genes that give TGCT an inherent sensitivity to apoptotic stimuli after exposure to DNA damaging agents. Studies on these genes in therapy-refractory cancers should provide further insight into the mechanisms of chemotherapy resistance. Furthermore, these genes are promising targets for a future targeted therapy of testis cancer.
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Koblenz, Germany. Hans.U.Schmelz@web.de
authors.forename: Hans U
authors.initials: HU
authors.lastname: Schmelz
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
authors.forename: Markus
authors.initials: M
authors.lastname: Stockinger
authors.forename: Christian
authors.initials: C
authors.lastname: Ruf
authors.forename: Andreas
authors.initials: A
authors.lastname: Martinscheck
authors.forename: Christoph
authors.initials: C
authors.lastname: Sparwasser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weidner
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D001706:Biopsy; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult