TY - JOUR
T1 - Intracellular distribution of β-catenin in human medulloblastoma cell lines with different degree of neuronal differentiation
AU - Salaroli, Roberta
AU - Russo, Alessandra
AU - Ceccarelli, Claudio
AU - Mina, Giorgia D.
AU - Arcella, Antonella
AU - Martinelli, Giuseppe N.
AU - Giangaspero, Felice
AU - Capranico, Giovanni
AU - Cenacchi, Giovanna
PY - 2007/2
Y1 - 2007/2
N2 - 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 β-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, β-catenin levels remained unchanged or were slightly reduced, but β-catenin translocated in the nucleus following APC gene siRNA silencing. In contrast, in the more differentiated D283MED cells, β-catenin levels increased about twofold while mainly maintaining the cytoplasmic and cell membrane localization. Cytoplasmic/nuclear localization of β-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/β-catenin pathway in neuronal differentiation in medulloblastoma.
AB - 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 β-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, β-catenin levels remained unchanged or were slightly reduced, but β-catenin translocated in the nucleus following APC gene siRNA silencing. In contrast, in the more differentiated D283MED cells, β-catenin levels increased about twofold while mainly maintaining the cytoplasmic and cell membrane localization. Cytoplasmic/nuclear localization of β-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/β-catenin pathway in neuronal differentiation in medulloblastoma.
KW - β-catenin
KW - Adenomatous polyposis coli (APC)
KW - Electron microscopy
KW - Medulloblastoma
KW - Small-interfering RNAs (siRNA)
UR - http://www.scopus.com/inward/record.url?scp=34147124194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34147124194&partnerID=8YFLogxK
U2 - 10.1080/01913120601169501
DO - 10.1080/01913120601169501
M3 - Article
C2 - 17455096
AN - SCOPUS:34147124194
VL - 31
SP - 33
EP - 44
JO - Ultrastructural Pathology
JF - Ultrastructural Pathology
SN - 0191-3123
IS - 1
ER -