Cigarette smoke condensate induces nuclear factor kappa-b activity and proangiogenic growth factors in aerodigestive cells.
OBJECTIVE
Aerodigestive cancer risk of both lung and head and neck cancers has been linked to the genotoxic effects of tobacco use. These effects include upregulation of nuclear factor kappa-B (NFkappaB) and its downstream products associated with both lung and head and neck cancer malignant progression.


METHODS
Bench Research.


METHODS
In the present study we examined the effects of cigarette smoke condensate on functional activation of NFkappaB in human papillomavirus (HPV)-transformed oral cavity cells (HOK 16B cells) and transformed bronchial epithelium (Beas2B cells) using the head and neck squamous cancer cell line, UMSCC 38, as a comparison. Luciferase reporter gene assays with two types of transiently transfected NFkappaB reporter genes were employed and downstream NFkappaB-dependent products, interleukin-6, interleukin-8, and vascular endothelial growth factor, were assayed by enzyme-linked immunosorbent assay.


RESULTS
All cell lines were able to dose dependently activate NFkappaB reporter genes after exposure to cigarette smoke condensate (P < .05). However, the HPV premalignant, transformed cell line had a much more robust NFkappaB response (3.45-fold) versus the squamous cancer cell line (1.62-fold) and SV40 transformed Beas2B (1.83). Both NFkappaB reporter genes had similar response curves.


CONCLUSIONS
This study demonstrates cigarette smoke products might be more potent promoters of an NFkappaB-dependent progression from HPV+ premalignancy to cancer rather than after tumors are established. Future studies should focus on abrogating NFkappaB increases during malignant progression and premalignancy. This might be even more relevant in the HPV+ patient with premalignancy.
Rohrer
Joseph
J
Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA. rohr0045@umn.edu
Wuertz
Beverly R K
BR
Ondrey
Frank
F
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology*; D017930:Genes, Reporter; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D015854:Up-Regulation
D016328:NF-kappa B; D012906:Smoke