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.
Materials and 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.