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Inhibition of breast cancer progression with Vitamin D compounds
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Wahler, Joseph. Inhibition of breast cancer progression with Vitamin D compounds. Retrieved from https://doi.org/doi:10.7282/T3RJ4MGP

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TitleInhibition of breast cancer progression with Vitamin D compounds
NameWahler, Joseph (author); Suh, Nanjoo (chair); Chen, Suzie (internal member); Cai, Li (internal member); Liu, Fang (internal member); Cohick, Wendie (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2015
Other Date2015-10 (degree)
SubjectPharmacology, Cellular and Molecular, Breast--Cancer--Treatment, Vitamin D
Extent1 online resource (xvi, 171 p. : ill.)
DescriptionEarly epidemiological studies have shown an inverse correlation of increased vitamin D3 to breast cancer. Since this discovery, many studies have linked 1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, and vitamin D analogs to decreased cell proliferation, invasion, and metastasis. The pharmacological dose of 1,25(OH)2D3 required to elicit a response can induce hypercalcemic toxicity. Therefore, non-calcemic vitamin D analogs, such as BXL0124, have been of interest in the inhibition of breast cancer. Breast cancer is a heterogeneous disease which proceeds through a natural progression, beginning with early hyperplasia and culminating in invasive or metastatic disease. Ductal carcinoma in situ (DCIS) is a non-malignant lesion of the breast with the potential to progress to invasive ductal carcinoma (IDC). Due to the implications of breast cancer stem cells (BCSCs) in breast cancer progression, we investigated the role of vitamin D compounds on these processes. We showed that BXL0124 inhibited the progression of DCIS to IDC in a model of breast cancer progression by maintaining critical DCIS structures through the modulation of matrix metalloproteinases transcription. In addition, BXL0124 treatment decreased cell proliferation and maintained vitamin D receptor (VDR) levels in tumors. VDR was expressed in a variety of clinical breast tumors and was lost during malignant transformation of normal mammary cells to pre-malignant histological types, suggesting vitamin D supplementation as a preventative agent due to higher VDR levels in normal breast tissue. Vitamin D compounds (125(OH)2D3 or BXL0124) reduced the growth and self-renewal of mammospheres, an assay which enriches for BCSCs. The putative CD44+/CD24-/low BCSC population was shifted to a population expressing higher CD24 in vitro and in vivo by treatment with BXL0124. Pluripotency genes such as CD44 and OCT4 were also repressed, contributing to the reduction in cell and tumor growth. We demonstrated the therapeutic potential of Gemini vitamin D analog BXL0124 on the inhibition of breast cancer progression and the ability of vitamin D compounds to repress the BCSC population in vitro and in vivo, potentially contributing to the effects on tumor progression.
NotePh.D.
NoteIncludes bibliographical references
Noteby Joseph Wahler
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3RJ4MGP
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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