Expression of inhibitor of apoptosis proteins in small- and non-small-cell lung carcinoma cells.
Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cells both initiate apoptotic signaling, resulting in caspase activation, after treatment with anti-cancer agents. However, in contrast to SCLC cells, NSCLC cells do not fully execute apoptosis. The apoptotic process in NSCLC cells seems to be blocked downstream of caspase activation, thus the failure of NSCLC cells to execute apoptosis could result from inhibition of active caspases by inhibitor of apoptosis proteins (IAPs). Here we investigate the mRNA and protein expression of IAPs in a panel of SCLC and NSCLC cell lines. The NSCLC cell lines had a stronger cIAP-2 expression at both mRNA and protein levels, while the SCLC cell lines had a higher level of XIAP protein. Expression of cIAP-1, cIAP-2, and XIAP, the most potent caspase inhibitors, was further investigated in three lung carcinoma cell lines after treatment with 8 Gy of ionizing radiation or etoposide (VP16). In response to treatment, the level of IAPs was not altered in a way that explained the differences in cellular chemo- and radiosensitivity. The intracellular localization of IAPs was analyzed in untreated and treated lung cancer cells. Surprisingly, we found that cIAP-2 was mainly detected in the mitochondrial fraction, although the function of this protein in mitochondria is unknown. No major relocalization of IAPs was observed after treatment. Taken together, these results indicate that IAPs alone are not the main factor responsible for the resistance of NSCLC cells to treatment.
Ekedahl
Jessica
J
Institute of Environmental Medicine, Department of Toxicology, Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden.
Joseph
Bertrand
B
Grigoriev
Maxim Yu
MY
Müller
Malin
M
Magnusson
Carina
C
Lewensohn
Rolf
R
Zhivotovsky
Boris
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002458:Cell Fractionation; D005047:Etoposide / Q000494:pharmacology; D005720:Gamma Rays; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D051636:X-Linked Inhibitor of Apoptosis Protein
D000972:Antineoplastic Agents, Phytogenic; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D005047:Etoposide; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases