TRAIL-R2 is not correlated with p53 status add 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 ol DR5, can be induced by either DNA damage or overexpression of a wild-type p53 t ransgene, suggesting a role for p53 in the death-signaling pathway. Further more, mutations in the death domain of TRAIL-R2 were repented in 10.6% of n on-small cell lung cancer (NSCLC) patients in a Korean population suggestin g a role for TRAIL-R2 in lung tumorigenesis. Materials and methods: To dete rmine the association between expression of TRAIL-R2 and p53 mutation statu s 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 als o sequenced the death domain of TRAIL-R2 in a total of 100 primary NSCLC. R esults: Lack of TRAIL-R2 expression was found in eight of 20 (40%) SCLC cel l lines and in eleven of 20 (55%) NSCLC cell lines. Interestingly, in prima ry NSCLC, TRAIL-R2 was overexpressed in seven (23%) of the 30 tumors tested , and all primary tumors expressed TRAIL-R2. No association was found betwe en the expression status of TRAIL-R2 and p53 mutation status in primary NSC LC tumors, SCLC cell lines or NSCLC cell lines. Further analysis of the dea th 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 a nd that mutations in the death domain of TRAIL-R2 play a minimal role in NS CLCs in white Americans.