Abstract
Cigarette smoking causes cell proliferation disorders, including lung cancers and emphysema. Although about 40% of lung cancers is associated with p53 mutations, the major part (60%) is of unknown etiology. Integration of transposable elements (TE) in or nearby cell cycle control genes may disrupt the cell cycle and lead to uncontrolled proliferation. This may lead to loss of lung tissue, as seen in emphysema, or to hyperplasia and the development of tumors.
To assess the effect of cigarette smoke extract (CSE) on the expression and transposition of LINE1 (L1), a human TE present in primary human lung fibroblast. The L1 open reading frame (ORF)-2 protein was detected in immunoblotting (Westerns). The applied CSE was used as a 1:10 dilution from a stock solution containing the smoke equivalent of 1 cigarette/25 ml.
Primary fibroblast cell lines (n=8) were cultured in RMPI without and with CSE for 10, 30, 60, 90 and 120 minutes. Resting cells did not express detectable levels of L1-ORF2. CSE induced a biphasic L1-ORF2 expression pattern: an immediate early maximum at 10-30 minutes and a second maximum after 120 minutes. This coincided with a complete inhibition on fibroproliferation.
We conclude that CSE induced the expression of L1-ORF2, a marker for transposable elements activity. The increased expression of L1-ORF2 implies an overall increased activity of TE, since the L1-transposition machinery is also used by other mobile elements. Uncontrolled transposition of TE may cause genetic changes and lead to genomic damage. Their involvement in smoking-induced proliferation-disorders should be envisaged to understand the heterogeneity observed in lung cancers and emphysema.
- © 2014 ERS