IngentaConnect The Gap Junctional Protein Connexin(Cx)43 in Testicular Cancer: i...

Abstract:

Carcinoma-in-situ (CIS) of the testis is known to be the pre-invasive stage of most human germ cell tumours (seminoma and non-seminoma), but the mechanisms leading to an increased pubertal proliferation of CIS cells after a long latency and to progression of CIS to an invasive malignancy are still not known. Additionally, CIS and seminoma have also been reported in equine testis (Veeramachaneni and Sawyer, 1998). The gap junctional protein and tumour suppressor gene connexin(cx)43 represents the predominant cx in human, canine and rodent testis so far and it is expected to play a key role for the regulation of both proliferation and differentiation of germ cells (spermatogonia and spermatocytes), and its gene- and protein-expression pattern is typical for the pubertal terminal differentiation of somatic Sertoli cells. Using cDNA-microarray analysis, in-situ hybridization (ISH), RT-PCR from tissue homogenate and semi-quantitative RT-PCR from well defined microdissected tubules with normal spermatogenesis, CIS, intratubular seminoma (ISe) and from seminoma cells from invasive seminoma we found a downregulation of cx43 starting in intratubular CIS, leading to a complete loss in most invasive seminoma cells. This indicates that regulation of cx43 expression takes place at transcriptional level confirming and expanding earlier studies of protein expression (Brehm et al., 2002). This reduction of cx43-expression suggests that an early intratubular derangement in cx43-gene expression and disruption of inter-cellular communication between Sertoli cells and/or Sertoli cells and pre-invasive tumour cells via cx43-gap junctions may play a role in the proliferation of CIS cells and seminoma cells and in the progression phase of testicular seminoma development. References

Veeramachaneni, D. N., and H. R.Sawyer, 1998: Carcinoma in situ and seminoma in equine testis. APMIS 106, 183–185.

Brehm R., A. Marks, R. Rey, S. Kliesch, M. Bergmann and K. Steger, 2002: Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous tubules infiltrated with carcinoma-in-situ or seminoma. J. Pathol. 197, 647–653.

Document Type: Research article

DOI: 10.1111/j.1439-0264.2005.00669_16.x

Affiliations: 1: Institute of Veterinary Anatomy, University of Giessen, Germany 2: Department of Urology, University of Muenster, Germany 3: Institute of Anatomy, University Hospital, Essen, Germany 4: Department of Pathology, University of Giessen, Germany

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The Gap Junctional Protein Connexin(Cx)43 in Testicular Cancer: its Loss Marks Progession from Carcinoma In Situ to Invasive Germ Cell Tumour