Radiobiologic response of medulloblastoma cell lines: involvement of beta-catenin?
Medulloblastoma (MB) is the most common brain malignancy in children. Whole neural axis irradiation is the treatment of choice, but it often results in long-term neurocognitive and developmental impairment. Only insights into MB biology will lead to improved therapeutic outcome. Wingless (WNT) signalling deregulation occurs in up to 25% of sporadic tumors, but the specific role of nuclear beta-catenin and its involvement in the radioresponse remains unsettled. Therefore we studied the gamma-radiation response of two MB cell lines from cellular and molecular points of view. Our data show that the p53 wild-type cell line is more sensitive to ionizing radiations (IR) than the p53 mutated line, but apoptosis is also induced in p53-mutated cells, suggesting an alternative p53-independent mechanism. In addition, this study is the first to demonstrate that gamma-rays trigger the WNT system in our in vitro models. Further studies are required to test if this could explain the radiosensitivity of MB and the favorable prognostic value of nuclear beta-catenin in this tumor.
Salaroli
Roberta
R
Dipartimento Clinico Scienze Radiologiche e Istocitopatologiche, "Alma Mater" Università di Bologna, Bologna, Italy.
Di Tomaso
Tiziano
T
Ronchi
Alice
A
Ceccarelli
Claudio
C
Cammelli
Silvia
S
Cappellini
Alessandra
A
Martinelli
Giuseppe Nicola
GN
Barbieri
Enza
E
Giangaspero
Felice
F
Cenacchi
Giovanna
G
D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D051176:beta Catenin