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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta Jan 2014

Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta

Legacy Theses & Dissertations (2009 - 2024)

1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …


Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy Jan 2014

Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy

Legacy Theses & Dissertations (2009 - 2024)

The accumulation of senescent cells during the process of aging has been implicated as causal in numerous age-related pathologies. Senescent cells adopt a secretory phenotype consisting of many factors including matrix remodeling enzymes, growth factors, cytokines, and chemokines. Their secretory nature is the primary reason that they are associated with disease, but it remains unclear why they become so inflammatory. Using primary human fibroblasts cultured to senescence, we mechanistically determined why senescent cells are such potent inducers of inflammation. Our findings indicate that the early production of the cytokine Interleukin 1-α (IL-1α) is central to this transition. We found that …