Intracellular distribution of beta-catenin in human medulloblastoma cell lines with different degree of neuronal differentiation.
Gene mutations impairing the functions of the WNT signaling transduction pathway have been found in approximately 15% of human sporadic medulloblastomas. To understand the functional role of the WNT pathway in medulloblastoma, we have investigated the intracellular distribution of beta-catenin in a series of 17 human medulloblastomas to correlate such expression with neuronal differentiation and in cultured cell models following functional silencing of the APC gene by small-interference RNA (siRNA). Transient siRNA transfection resulted in a 50% reduction of the APC gene product levels in both DAOY and D283MED cell lines. In the former, less-differentiated cell line, beta-catenin levels remained unchanged or were slightly reduced, but beta-catenin translocated in the nucleus following APC gene siRNA silencing. In contrast, in the more differentiated D283MED cells, beta-catenin levels increased about twofold while mainly maintaining the cytoplasmic and cell membrane localization. Cytoplasmic/nuclear localization of beta-catenin was present in 12 of 17 cases of medulloblastoma with a prevalent distribution in the classic, 6/7 cases, and large cell/anaplastic variant, 4/4 cases. The nodular/desmoplastic lesions showed strongly positivity in the cell membrane mainly of intranodular cells with advanced neuronal differentiation. These observations support an important functional role of WNT/beta-catenin pathway in neuronal differentiation in medulloblastoma.
Salaroli
Roberta
R
Clinical Department of Radiological and Histopathological Sciences, Bologna, Italy.
Russo
Alessandra
A
Ceccarelli
Claudio
C
Mina
Giorgia D
GD
Arcella
Antonella
A
Martinelli
Giuseppe N
GN
Giangaspero
Felice
F
Capranico
Giovanni
G
Cenacchi
Giovanna
G
D021581:Active Transport, Cell Nucleus; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin