637

BID

FP497;BH3 interacting domain death agonist;BID;BH3 interacting domain death agonist

BH3-interacting domain death agonist|BID isoform ES(1b)|BID isoform L(2)|BID isoform Si6|Human BID coding sequence|apoptic death agonist|desmocollin type 4|p22 BID

22q11.1

protein-coding

BACKGROUND: childhood ependymoma remains a major therapeutic challenge despite surgery, chemotherapy, and irradiation. We hypothesized that p53 function might be abrogated in ependymomas and implicated in their resistance to anti-cancer therapy. PROCEDURE: Primary ependymomas at diagnosis or relapse from 24 childrenwere analyzed for p53 pathway, using a functional assay in yeast, RT-PCR, Western blot analysis, and/or immunohistochemistry for TP53 mutation, p14(ARF) deletion and promoter hypermethylation, MDM2 and PAX5 expression, respectively. p53-mediated response to radiation-induced DNA damage was evaluated using Western blot and flow cytometry analysis in two ependymoma xenograft models, IGREP37 andIGREP83, derived from primary anaplastic childhood ependymomas. RESULTS: No TP53, MDM2, p14(ARF), PAX5 gene abnormalities were detected in the primary ependymomastumors and xenografts tested. Interestingly, despite the lack of these abnormalities, p53 induced p21-mediated G(1) growth arrest in response to irradiation was altered in the IGREP37 xenograft tumors. Although irradiation induced necrosis and apoptotic cell death, IGREP37 tumors were moderately sensitive to radiation therapy in vivo. In contrast, irradiation yielded significant tumor growth delays and tumor regressions in the p53 functional IGREP83 xenografts. CONCLUSION: Alterations in p53-mediated growth arrest in ependymomas might be implicated in the radio-resistance of these tumors and demand further evaluation.