Date on Master's Thesis/Doctoral Dissertation

5-2019

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Li, Chi

Committee Co-Chair (if applicable)

Beverly, Levi

Committee Member

Beverly, Levi

Committee Member

Clark, Geoffrey

Committee Member

Clem, Brian

Committee Member

Mitchell, Robert

Author's Keywords

Paraoxonase 2; PON2; cancer; non-small cell lung carcinoma; NSCLC

Abstract

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 is required for NSCLC proliferation, but dispensable for normal mouse development and non-transformed cell proliferation. These observations highlight PON2 as a potential therapeutic target against NSCLC.

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