title: Transition from preinvasive carcinoma in situ to seminoma is accompanied by a reduction of connexin 43 expression in Sertoli cells and germ cells.
abstract: Carcinoma in situ (CIS) represents the preinvasive stage of human germ cell tumors, but the mechanism leading to pubertal proliferation and invasive malignancy remains unknown. Among testicular gap junctional proteins, connexin 43 (Cx43) represents the predominant Cx, and, previously, an inverse correlation between synthesis of Cx43 protein and progression of tumor development was detected. In the present study, using cDNA microarray analysis, in situ hybridization, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) from tissue homogenates, RT-PCR from microdissected tubules with normal spermatogenesis and CIS, and seminoma cells from invasive seminoma, we asked whether reduction of Cx43 protein is accompanied by a change of Cx43 transcripts. We detected a significant downregulation of Cx43 at mRNA level in Sertoli and germ cells starting in seminiferous tubules infiltrated with CIS and resulting in a complete loss in seminoma cells. It was demonstrated, that downregulation of Cx43 expression in neoplastic human testis takes place at the transcriptional level and starts in CIS. This reduction of Cx43 expression further suggests that early intratubular derangement in Cx43 gene expression and disruption of intercellular communication between Sertoli cells and/or Sertoli and preinvasive tumor cells may play a role in the progression phase of human seminoma development.
authors.affiliation: Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Giessen, Germany. Ralph.H.Brehm@vetmed.uni-giessen.de
authors.forename: Ralph
authors.initials: R
authors.lastname: Brehm
authors.forename: Christina
authors.initials: C
authors.lastname: Rüttinger
authors.forename: Petra
authors.initials: P
authors.lastname: Fischer
authors.forename: Isabella
authors.initials: I
authors.lastname: Gashaw
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Sabine
authors.initials: S
authors.lastname: Kliesch
authors.forename: Rainer M
authors.initials: RM
authors.lastname: Bohle
authors.forename: Klaus
authors.initials: K
authors.lastname: Steger
authors.forename: Martin
authors.initials: M
authors.lastname: Bergmann
mesh_terms: D000328:Adult; D002278:Carcinoma in Situ / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D018031:Connexin 43 / Q000096:biosynthesis*; D017629:Gap Junctions; D015972:Gene Expression Regulation, Neoplastic; D005854:Germ Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D018239:Seminoma / Q000378:metabolism / Q000473:pathology*; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D018031:Connexin 43