Aberrant nuclear factor-kappaB activity and its participation in the growth of human malignant astrocytoma.
OBJECTIVE
It has been suggested that nuclear factor (NF)-kappaB, a pleiotropic transcription factor, controls cell proliferation. The authors examined NF-kappaB activity and its participation in the growth of human malignant astrocytoma.


METHODS
The authors examined NF-kappaB activity in human malignant astrocytoma cell lines and high-grade astrocytoma tissues by using electrophoretic mobility shift assays and immunohistochemical studies, respectively. In addition, messenger (m)RNA expression of p50 and RelA, which are representative subunits of NF-kappaB, and IkappaBalpha, which is a representative inhibitory protein of NF-KB, were analyzed using Northern blot hybridization in the astrocytoma cell lines. Furthermore, alterations in DNA synthesis and cell growth in the astrocytoma cell lines were examined after inhibition of NF-kappaB activity by RelA antisense oligodeoxynucleotide. The authors found NF-kappaB activity in all astrocytoma cell lines and high-grade astrocytoma tissues that were examined, but not in the fetal astrocyte strain or in normal cerebral tissue. Expression of p50, RelA, and IkappaBalpha mRNA was found in the fetal astrocyte strain and normal adult brain tissue, in addition to the astrocytoma cell lines. The relative levels of expression of these mRNAs were similar among these cell lines, the cell strain, and normal tissue. The RelA antisense oligodeoxynucleotide specifically reduced the levels of RelA mRNA expression and NF-kappaB activity in the astrocytoma cell lines, thus significantly inhibiting their DNA synthesis and cell growth.


CONCLUSIONS
Human malignant astrocytoma cells have aberrant NF-KB activity, which promotes their growth. This activity is not associated with aberrant expression of p50 and RelA.
Nagai
Shoichi
S
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, Japan. shoichi@chive.ocn.ne.jp
Washiyama
Kazuo
K
Kurimoto
Masanori
M
Takaku
Akira
A
Endo
Shunro
S
Kumanishi
Toshiro
T
D000367:Age Factors; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001254:Astrocytoma; D001921:Brain / Q000166:cytology; D001932:Brain Neoplasms; D002455:Cell Division / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D005333:Fetus / Q000166:cytology; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA