Abrogation of cyclin D1 expression predisposes lung cancer cells to serum deprivation-induced apoptosis
Driscoll, B.; Buckley, S.; Barsky, L.; Weinberg, K.; Anderson, K.D.; Warburton, D.
American Journal of Physiology 276(4): L679-L687
1999
ISSN/ISBN: 0002-9513 PMID: 10198366 Document Number: 509956
Cyclin D1 antisense (D1AS)-transfected lung epithelial cell lines were serum deprived and then analyzed for three hallmarks of apoptosis: appearance of single-strand DNA breaks, alteration of apoptosis-related protein expression, and induction of chromatin condensation. Single-strand DNA breaks appeared at significant levels 24 h after serum deprivation, whereas induction of chromatin condensation was observed after 72 h. The antioxidants dimethyl sulfoxide, ascorbate, and glutathione, as well as insulin-like growth factor-I, inhibited induction of DNA damage in this assay. Additionally, proliferating cell nuclear antigen expression is completely suppressed in the D1AS cells, indicating a mechanism to explain the reduced capacity for DNA repair. Increased expression of cyclin D1, which is a common lesion in lung cancer, may thus prevent induction of apoptosis in an oxidizing and growth factor-poor environment. Reducing cyclin D1 expression in lung cancer cells by expression of D1AS RNA disrupted these protective pathways. Reprinted by permission of the publisher.