Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues

Glendon M. Zinser, Mark Suckow, Jo Ellen Welsh

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

The Vitamin D receptor (VDR) and its ligand, 1,25(OH)2D 3, regulate cell proliferation, differentiation and apoptosis in vitro, yet the physiological significance of this regulation is unclear. In these studies, we used VDR knockout (VDRKO) mice to examine the impact of VDR on chemical carcinogen-induced tumorigenesis in vivo. Wild type (WT) and VDRKO littermates were fed a high calcium diet to prevent disturbances in calcium homeostasis and were gavaged with dimethylbenzanthracence (DMBA) using a protocol designed to induce mammary tumors. Compared to WT littermates, VDRKO mice exhibited an increased incidence of mammary gland hyperplasia and a higher percentage of hormone independent tumors with squamous differentiation. VDR ablation also significantly enhanced tumor development in epidermis and lymphoid tissues, but did not affect tumor development in ovary, uterus, lung or liver. These data indicate that VDR ablation alters susceptibility to DMBA-induced carcinogenesis in a tissue specific fashion, and provide support that optimal VDR signaling may act to suppress tumorigenesis.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume97
Issue number1-2
DOIs
StatePublished - Oct 2005

Bibliographical note

Funding Information:
This research was supported by grants to JW from the National Institutes of Health (CA69700) and a Dissertation award to GMZ from the Susan G. Komen Breast Cancer Foundation (DISS 0100302). The authors are grateful to Emily Tribble for her assistance with tissue processing and histology, and to Valerie Schroeder and Lindsay Barnett of the Freimann Life Science Center at the University of Notre Dame for care of the animal colonies. Histopathological assessment of mammary tumors by Dr. Robert Cardiff at the UC Davis Mutant Mouse Resource is greatly appreciated.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Breast cancer
  • DMBA
  • Mammary
  • Vitamin D receptor

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