Abstract

During the previous grant period, the PI demonstrated that 1,25 dihydroxyvitamin D3 (1,25D) induces typical morphologic, biochemical and molecular features of apoptosis in MCF-7 human breast cancer cells. The overall hypothesis is the 1,25D and its nuclear receptor, the vitamin D receptor (VDR) coordinately regulate mammary epithelial cell proliferation and apoptosis. This renewal application will investigate 1,25D signaling in relation to proliferation and apoptosis of normal and transformed mammary epithelial cells.
Three specific aims will be addressed concurrently: 1. Characterized downstream signaling from VDR leading to apoptosis in MCF-7 cells and a vitamin D resistant variant. 2. Examine transcriptional regulation of the human VDR promoter in mammary cells, and to provide evidence of a role for VDR in mammary gland function in vivo. These three diverse specific aims will comprehensively examine the role of 1,25D and the VDR in regulation of proliferation and apoptosis of mammary epithelial cells using cellular, molecular and whole animal approaches.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA069700-10
Application #
6758562
Study Section
Nutrition Study Section (NTN)
Program Officer
Ross, Sharon A
Project Start
1995-09-30
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
10
Fiscal Year
2004
Total Cost
$282,300
Indirect Cost

  Institution

Name
University of Notre Dame
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556

  Publications

Welsh, JoEllen (2018) Vitamin D and breast cancer: Past and present. J Steroid Biochem Mol Biol 177:15-20
Welsh, JoEllen (2017) Function of the vitamin D endocrine system in mammary gland and breast cancer. Mol Cell Endocrinol 453:88-95
Matthews, Donald G; D'Angelo, Joseph; Drelich, Jordan et al. (2016) Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial density. J Steroid Biochem Mol Biol 164:299-308
Beaudin, Sarah G; Robilotto, Samantha; Welsh, JoEllen (2015) Comparative regulation of gene expression by 1,25-dihydroxyvitamin D3 in cells derived from normal mammary tissue and breast cancer. J Steroid Biochem Mol Biol 148:96-102
Rhieu, Steve Y; Annalora, Andrew J; LaPorta, Erika et al. (2014) Potent antiproliferative effects of 25-hydroxy-16-ene-23-yne-vitamin D? that resists the catalytic activity of both CYP27B1 and CYP24A1. J Cell Biochem 115:1392-402
LaPorta, Erika; Welsh, JoEllen (2014) Modeling vitamin D actions in triple negative/basal-like breast cancer. J Steroid Biochem Mol Biol 144 Pt A:65-73
Keith, Meggan E; LaPorta, Erika; Welsh, JoEllen (2014) Stable expression of human VDR in murine VDR-null cells recapitulates vitamin D mediated anti-cancer signaling. Mol Carcinog 53:286-99
Narvaez, C J; Simmons, K M; Brunton, J et al. (2013) Induction of STEAP4 correlates with 1,25-dihydroxyvitamin D3 stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue. J Cell Physiol 228:2024-36
Welsh, JoEllen (2012) Cellular and molecular effects of vitamin D on carcinogenesis. Arch Biochem Biophys 523:107-14
Welsh, JoEllen; Zinser, Lindsay N; Mianecki-Morton, Laurel et al. (2011) Age-related changes in the epithelial and stromal compartments of the mammary gland in normocalcemic mice lacking the vitamin D3 receptor. PLoS One 6:e16479

Showing the most recent 10 out of 42 publications