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Full-Text Articles in Pharmacology

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt May 2019

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …


Pbrm1 Regulates Stress Response In Epithelial Cells, Elizabeth G. Porter, Alisha Dhiman, Basudev Chowdhury, Benjamin C. Carter, Hang Lin, Jane C. Stewart, Majid Kazemian, Michael K. Wendt, Emily C. Dykhuizen Apr 2019

Pbrm1 Regulates Stress Response In Epithelial Cells, Elizabeth G. Porter, Alisha Dhiman, Basudev Chowdhury, Benjamin C. Carter, Hang Lin, Jane C. Stewart, Majid Kazemian, Michael K. Wendt, Emily C. Dykhuizen

Department of Biochemistry Faculty Publications

Polybromo1 (PBRM1) is a chromatin remodeler subunit highly mutated in cancer, particularly clear cell renal carcinoma. PBRM1 is a member of the SWI/SNF subcomplex, PBAF (PBRM1-Brg1/Brm-associated factors), and is characterized by six tandem bromodomains. Here we establish a role for PBRM1 in epithelial cell maintenance through the expression of genes involved in cell adhesion, metabolism, stress response, and apoptosis. In support of a general role for PBRM1 in stress response and apoptosis, we observe that loss of PBRM1 results in an increase in reactive oxygen species generation and a decrease in cellular viability under stress conditions. We find that loss …