Virchows Archiv

, Volume 437, Issue 5, pp 501–507

In situ mRNA hybridization analysis and immunolocalization of the vitamin D receptor in normal and carcinomatous human colonic mucosa: relation to epidermal growth factor receptor expression

  • Yuri Sheinin
  • Klaus Kaserer
  • Friedrich Wrba
  • Etienne Wenzl
  • Stefan Kriwanek
  • Meinrad Peterlik
  • Heide S. Cross
Original Article

DOI: 10.1007/s004280000275

Cite this article as:
Sheinin, Y., Kaserer, K., Wrba, F. et al. Virchows Arch (2000) 437: 501. doi:10.1007/s004280000275

Abstract.

There is evidence that vitamin D receptor (VDR)-mediated action of 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) could limit colon cancer cell growth particularly when induced by activation of the epidermal growth factor receptor (EGFR). We therefore wanted to ascertain the relevance of this observation for human colon cancerogenesis. Utilizing in situ mRNA hybridization and immunocytochemical techniques, we analyzed cell-specific expression of VDR and EGFR in normal and malignant human colonic mucosa. In normal mucosa, VDR positivity is weak and observed only in a small number of luminal surface colonocytes. In contrast, EGFR expression at a relatively high level is also found in cells at the crypt base. The number of VDR-positive colonocytes increases remarkably during tumor progression. It reaches its maximum in low grade adenocarcinomas and returns to lower levels in highly malignant cancers. In both low- and high grade carcinomas, the great majority of tumor cells contain the EGFR message. The relative abundance of EGFR over VDR in normal mucosa and in high grade carcinomas would create a situation in which mitogenic effects from EGFR activation are only ineffectively counteracted by signaling from 1α,25-(OH)2D3/VDR. In contrast, in well to moderately differentiated tumors, upregulation of VDR could retard further tumor progression.

Colon adenocarcinoma Growth control Differentiation Steroid hormone receptors 1,25-Dihydroxyvitamin D3

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Yuri Sheinin
    • 1
  • Klaus Kaserer
    • 2
  • Friedrich Wrba
    • 2
  • Etienne Wenzl
    • 3
  • Stefan Kriwanek
    • 4
  • Meinrad Peterlik
    • 1
  • Heide S. Cross
    • 1
  1. 1.Department of Pathophysiology, Waehringer Guertel 18–20, 1090 Vienna, Austria
  2. 2.Department of Clinical Pathology, Waehringer Guertel 18–20, 1090 Vienna, Austria
  3. 3.Department of Surgery, University of Vienna Medical School, Waehringer Guertel 18–20, 1090 Vienna, Austria
  4. 4.Department of Surgery II, Krankenhaus Rudolfsstiftung, Juchgasse 25, 1030 Vienna, Austria