Breast Tumor Development and Cigarette Smoking: Accelerated Tumor Development in Calcium Independent Phospholipase A 2 γ Deficient Mice

The phospholipase A 2 (PLA 2 ) family of enzymes are responsible for cleavage of membrane phospholipids, releasing a free fatty acid and lysophospholipid. Various PLA 2 dependent pathways are important in regulation of cell proliferation, differentiation, motility, and immune responses which can all be altered during tumor development and progression. Calcium independent PLA 2 (iPLA 2 ) enzymes are responsible for phospholipid remodeling as well as release of arachidonic acid or lysophosphatidic acid (LPA) which play major roles in downstream signaling pathways. The most commonly studied iPLA 2 enzymes are iPLA 2 β and iPLA 2 γ, but their role in cancer development remains unknown. To determine what effects cigarette smoke exposure had on mammary tissue from wild type and iPLA 2 γ deficient mice, we exposed six month old females to cigarette smoke using the SCIREQ InExpose system for up to six months. Mammary tissue was removed and snap frozen for biochemistry or stored in formalin for immunohistochemical analysis. Following three and six months of cigarette smoke exposure, wild type mice showed atypical ductal hyperplasia. In comparison, the iPLA 2 γ knockout mice developed ductal carcinoma in situ following three months of cigarette smoke exposure. Recent studies from our lab have determined that iPLA 2 γ deletion in mice results in alterations of cytokine expression implicated in breast tumor progression when compared to wild type mice. Changes in cytokine expression may elucidate the mechanism by which iPLA 2 γ deficient mice develop tumors more rapidly than wild type mice in the presence of cigarette smoking. Support or Funding Information Saint Louis University Presidents Research Fund