Date of Award




Document Type


Degree Name

Doctor of Philosophy (PhD)


Department of Biomedical Sciences

Content Description

1 online resource (xv, 137 pages) : illustrations (some color)

Dissertation/Thesis Chair

JoEllen Welsh

Committee Members

Martin Tenniswood, Ramune Reliene, Doug Conklin, Andre Melendez


Breast cancer, Glutamate transport, Glutamine metabolism, Human mammary epithelial cells, Vitamin D, Cellular signal transduction, Epithelial cells, Mammary glands, Glutamine, Glutamic acid, Genetic regulation, Telomerase, Breast

Subject Categories

Molecular Biology


Exposure to 1,25-Dihydroxyvitamin D (1,25D) decreases proliferation and induces differentiation in telomerase-immortalized human mammary epithelial (hTERT-HME1) cells. The studies described here addressed the mechanisms by which these effects are exerted. Microarray experiments were used to identify a subset of metabolic genes and pathways that are altered by 1,25D. In particular, genes involved in glutamate and glutamine utilization, including SLC1A1 and GLUL, were studied. Interestingly, qPCR analysis in a panel of six cell lines, representing either normal epithelial tissue or breast cancer, demonstrated diverse gene expression responses to 1,25D. In an isogenic model of mammary cell transformation, 1,25D altered gene expression in immortalized HME cells and in HME cells expressing SV40 (HME-LT), but not in HME-LT cells expressing oncogenic RAS (HME-PR).