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Activation of AP‐1 Signaling Pathway in Breast Epithelial Cells by Direct and Secondhand Cigarette Smoke
Author(s) -
Mukherjee Shyamali,
Das Salil K
Publication year - 2010
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.24.1_supplement.704.4
Subject(s) - cyclin d1 , secondhand smoke , tobacco smoke , western blot , downregulation and upregulation , cell growth , cigarette smoke , breast cancer , cancer research , medicine , chemistry , physiology , cancer , cell cycle , environmental health , gene , biochemistry
AP‐1, a dimeric protein complex composed of Jun and Fos proteins, plays a key role in the control of cell death, proliferation and transformation. Several epidemiological studies have linked cigarette smoking to breast cancer, particularly in young women. Due to difficulties in conducting such studies in humans, we have developed and standardized a smoke exposure model system for human breast cell lines. This is a modified version of CULTEX cell culture smoke exposure system using the principle of the air/liquid exposure technique. Cells ( MCF10, MCF 12A and MCF 12F) were grown in culture media (DMEM/F‐12) and exposed to both direct and secondhand smoke generated from 1R3F cigarettes in a THRI MS‐SS smoke exposure systems. A sham control group was also used where cells were exposed to the same environmental condition without smoke exposure. Cells were isolated after 2 days and western blot analysis was performed to determine whether smoke exposure causes any change in the Jun and Fos family protein levels. Both direct and secondhand smoke exposure caused a significant activation of AP‐1 transcription factors associated with an increase in the protein level of Fos. Furthermore, an upregulation of cyclin D1 and PCNA was observed. Both direct and secondhand cigarette smoke exposure caused a significant activation of AP‐1 signaling pathway in all three breast cell lins. (Supported by FAMRI Clinical Innovator Award # 062415).