Transcriptional expression of survivin and its splice variants in brain tumors in humans.
OBJECTIVE
Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-deltaEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing quantitative reverse transcription-polymerase chain reaction. The correlation between transcript expression levels and pathological findings were also analyzed.


METHODS
Transcription levels were measured using primer pairs specific for survivin and either of its splice variants and were normalized to the glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested, glioblastoma cell lines showed the highest levels of survivin expression. Among brain tumor samples studied, survivin was preferentially expressed in malignant brain tumors and gliomas. The relative expression level of survivin-deltaEx3/survivin was significantly higher in malignant than in benign brain tumor samples. Expression patterns were dominant for survivin-deltaEx3 in malignant brain tumors and dominant for survivin-2B in benign ones. A significant linear correlation between survivin mRNA expression and MIB-1 labeling index was demonstrated in all brain tumor samples.


CONCLUSIONS
The authors' results indicate that quantifying the levels of survivin and its splice variants is useful for the prediction of the cell biological malignancy of gliomas, independent of their pathological features.
Department of Neurosurgery, Central Clinical Laboratory, Osaka Medical College, Takatsuki City, Osaka, Japan.
Yoshitaka
Y
Yamada
Toshihiko
T
Kuroiwa
Toshimasa
T
Nakagawa
Yoshinaga
Y
Kajimoto
Takehiko
T
Dohi
Haruhito
H
Azuma
Motomu
M
Tsuji
Kazuhiro
K
Kami
Shin-Ichi
S
Miyatake
D000974:Antibodies, Antinuclear / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005910:Glioma / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins; D012313:RNA; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014158:Transcription, Genetic / Q000235:genetics*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; C107489:BIRC5 protein, human; D004274:DNA, Recombinant; D051034:Inhibitor of Apoptosis Proteins; C440408:MIB-1 antibody; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C034477:RNA primers; D012333:RNA, Messenger; D000077022:Survivin; D012313:RNA