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PEDF Reduction Induced by Cigarette Smoke: A Potential Role for Breast Tumor Development
Author(s) -
Kispert Shan E,
McHowat Jane
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.698.12
Subject(s) - pedf , breast cancer , medicine , atypia , metastasis , pathology , immunohistochemistry , cancer , angiogenesis , hyperplasia , mammary gland , oncology , cancer research , physiology
There are many risk factors for cancer development and subsequent metastasis which include lifestyle choices such as diet, alcohol, and cigarette smoking. Smoking has been linked to several cancers including breast cancer. Many cohort studies have described the link between patients with breast cancer and those with long term smoking history. Despite the claim of correlation, the mechanism by which cigarette smoke alters breast epithelial cells and contributes to tumor cell growth and metastasis remains undefined. Pigment epithelium‐derived factor (PEDF) is a potent anti‐angiogenic factor and is shown to have inhibitory effects in numerous cancers. PEDF is often decreased or absent in tumor tissue when compared to surrounding stroma and its absence has resulted in cellular atypia. Female PEDF knockout mice show histologic changes in the breast at six months of age consistent with atypical ductal hyperplasia. We have shown that cigarette smoke exposure of breast tumor cells resulted in decreased PEDF expression. In order to assess the effects of cigarette smoke on the breast in‐vivo , we exposed six month old female mice to cigarette smoke using the SCIREQ inExpose system for up to six months and harvested mammary tissue for histological and biochemical analysis. Histological analysis revealed changes that include atypical epithelial growth in mammary tissue from mice exposed to six months of cigarette smoke when compared to those exposed to room air only. Immunohistochemistry showed increases in expression of proteins commonly upregulated in breast cancer including Ki‐67, VEGF, and COX‐2 in mammary tissue exposed to six months of smoking when compared to room air controls. Smoke exposure also caused a decrease in PEDF expression when compared to room air tissue. We have shown here for the first time that cigarette smoke alters the histology of the mammary tissue in mice and alters expression of important markers involved in human breast tumor development and progression. Support or Funding Information Presidents Research Fund Saint Louis University School of Medicine