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Concordant Relationship of Anti-Apoptotic X-IAP Expression with Accelerated Lung Cancer Cell Growth Phenotypes FREE TO VIEW

King F. Kwong, MD*; Lindsay B. Cooper, BS; Mark J. Krasna, MD
Author and Funding Information

Greenebaum Cancer Center, University of Maryland, Baltimore, MD


Chest. 2004;126(4_MeetingAbstracts):732S. doi:10.1378/chest.126.4_MeetingAbstracts.732S-a
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PURPOSE:  Apoptosis pathways are highly conserved even in cancer cells but can be detrimentally altered. We have previously shown that pro-apoptotic Caspase-3 protein expression and activity are greater in slower-growing lung cancer cells compared to faster-growing phenotypes. Members of the IAP protein family, such as X-IAP, are responsible for direct inhibition of the Caspase cascade, thus exerting an anti-apoptosis, proliferating effect in cells. The purpose of this study is to identify in lung cancer cells of differing growth phenotypes whether X-IAP expression correlates with cancer cell growth and its relationship to Caspase expression.

METHODS:  Cytosolic fractions from non-small cell lung cancer cell lines (A549, Calu, and NCI-H596) and HeLa cells were isolated and equivalent protein amounts from each lung cancer cell line and from HeLa cells were separated by 1-D gel electrophoresis and subjected to Western immunoblotting using antibodies monospecific for Caspase-3 protein or for X-IAP protein. Relative protein expression was analyzed by digital densitometry.

RESULTS:  A549 cells have the fastest doubling times (8 hr), followed by Calu (30 hr) and H596 (27 hr) cells. HeLa cell growth is similar to A549. Western immunoblotting confirmed the presence of greater Caspase-3 in H596 and Calu than in A549. It also demonstrated a significantly higher level of X-IAP expression in A549 cells than in the slower-growing phenotypes. X-IAP and Caspase-3 protein expression in HeLa cells were comparable to the highly replicative A549 lung cancer cells.

CONCLUSION:  Intrinsic X-IAP expression is inversely related to Caspase-3 expression in all cases. X-IAP levels are greater in the faster-growing A549 cells in contrast to the slower-growing H596 and Calu cells. HeLa cells demonstrated Caspase-3 and X-IAP protein expression patterns mirroring that of A549.

CLINICAL IMPLICATIONS:  Increased X-IAP expression and concommitant down regulation of Caspase-3 may represent critical defects in the cell-cycle control pathway of lung cancer cells. Novel therapeutics directed towards greater expression of Caspase-3 and knock-down of X-IAP activity may possibly retard cellular proliferation and induce irreversible cell death in lung cancer cells.

DISCLOSURE:  K.F. Kwong, None.

Monday, October 25, 2004

2:30 PM- 4:00 PM




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