Frequent gene amplification and overexpression of decoy receptor 3 in glioblastoma.
The decoy receptor 3 (DcR3) gene is amplified at high frequency in human lung, colon, and liver cancers. DcR3 has been demonstrated to produce a secreted member of the tumor necrosis factor receptor superfamily that negatively regulates Fas-mediated apoptosis. In this study we examined DcR3 gene amplification, DcR3 mRNA expression, and DcR3 protein expression in 46 human astrocytic brain tumors by quantitative genomic PCR, quantitative reverse transcription-PCR, and immunohistochemistry, respectively. The DcR3 gene amplification was detected in none of 6 (0%) low-grade astrocytomas, 1 of 16 (6%) anaplastic astrocytomas, and 6 of 24 ( 25%) glioblastomas. Six of 7 (86%) cases with gene amplification exhibited both mRNA overexpression and/or protein overexpression, suggesting that DcR3 mRNA and protein were expressed more abundantly in the cases with gene amplification. We thus concluded that high DcR3 mRNA expression and protein expression may be positively related to the gene amplification in astrocytic brain tumors, especially glioblastomas. Further, we speculated that the DcR3 gene amplification with overexpression may be responsible for malignant features in glioblastomas.
Arakawa
Yasuaki
Y
Department of Neurosurgery, Toyama City Hospital, 2-1 Imaizumi-Hokubumachi, 939-8511, Toyama, Japan.
Tachibana
Osamu
O
Hasegawa
Mitsuhiro
M
Miyamori
Tadao
T
Yamashita
Junkoh
J
Hayashi
Yutaka
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002648:Child; D005260:Female; D005784:Gene Amplification / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human