TY - JOUR
T1 - Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion
AU - Tsunoda, Keishi
AU - Kitange, Gaspar
AU - Anda, Takeo
AU - Shabani, Hamisi Kimaro
AU - Kaminogo, Makio
AU - Shibata, Shobu
AU - Nagata, Izumi
PY - 2005/12
Y1 - 2005/12
N2 - Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-κB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-κB in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-κB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-κB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12- myristate-13-acetate (PMA)-induced RelA/NF-κB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-κB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-κB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.
AB - Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-κB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-κB in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-κB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-κB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12- myristate-13-acetate (PMA)-induced RelA/NF-κB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-κB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-κB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.
KW - Glioma
KW - Invasion
KW - Migration
KW - NF-κB
KW - u-PA
UR - http://www.scopus.com/inward/record.url?scp=33750082098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750082098&partnerID=8YFLogxK
U2 - 10.1007/s10014-005-0186-1
DO - 10.1007/s10014-005-0186-1
M3 - Article
C2 - 18095109
AN - SCOPUS:33750082098
SN - 1433-7398
VL - 22
SP - 79
EP - 87
JO - Brain Tumor Pathology
JF - Brain Tumor Pathology
IS - 2
ER -