TRAIL-R2 is not correlated with p53 status and is rarely mutated in non-small cell lung cancer.
BACKGROUND
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors play an important role in regulating apoptosis. Recently, it was shown that the expression of TRAIL-R2, also known as KILLER, Trick or DR5, can be induced by either DNA damage or overexpression of a wild-type p53 transgene, suggesting a role for p53 in the death-signaling pathway. Furthermore, mutations in the death domain of TRAIL-R2 were reported in 10.6% of non-small cell lung cancer (NSCLC) patients in a Korean population, suggesting a role for TRAIL-R2 in lung tumorigenesis.


METHODS
To determine the association between expression of TRAIL-R2 and p53 mutation status in lung cancers, we compared the two events in 20 small-cell lung cancer (SCLC) cell lines, 20 NSCLC cell lines, and 30 primary NSCLC tumors. We also sequenced the death domain of TRAIL-R2 in a total of 100 primary NSCLC.


RESULTS
Lack of TRAIL-R2 expression was found in eight of 20 (40%) SCLC cell lines and in eleven of 20 (55%) NSCLC cell lines. Interestingly, in primary NSCLC, TRAIL-R2 was overexpressed in seven (23%) of the 30 tumors tested, and all primary tumors expressed TRAIL-R2. No association was found between the expression status of TRAIL-R2 and p53 mutation status in primary NSCLC tumors, SCLC cell lines or NSCLC cell lines. Further analysis of the death domain of TRAIL-R2 failed to identify any mutation in 100 primary NSCLC tumors.


CONCLUSIONS
Our data indicate that the expression profile of TRAIL-R2 is significantly different in lung cancer cell lines and primary tumors, that the expression of TRAIL-R2 is independent from p53 mutation status and that mutations in the death domain of TRAIL-R2 play a minimal role in NSCLCs in white Americans.
Wu
W G
WG
Molecular Biology Laboratory, Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Soria
J C
JC
Wang
L
L
Kemp
B L
BL
Mao
L
L
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009363:Neoplasm Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human