Distinct expression of Survivin splice variants in breast carcinomas.
Survivin, a member of the inhibitor apoptosis family, is expressed in several human tumours, and its expression is regulated by p53. Recently, three alternative splice variants (Survivin-2B, Survivin-deltaEx3 and Survivin-3B), differing in their antiapoptotic properties, were identified. To date, little is known about the expression of all Survivin splice variants in breast cancer, particularly the recently identified Survivin-3B variant. In this study, we show that all Survivin transcripts were expressed in breast tumour cell lines and breast carcinomas, with a very weak expression detected in adjacent normal tissue. Frequency of proapoptotic Survivin-2B was significantly higher in small tumour size (p=0.026) and was inversely associated with axillary node positive carcinomas (p=0.004). In contrast, Survivin-3B was more frequent in high-grade carcinomas (p=0.004). Correlation with p53 status revealed that Survivin-3B was significantly more frequent in carcinomas with p53 gene mutation (p=0.036). After neoadjuvant chemotherapy, a significant reduction in the percentage of expressing Survivin (p=0.016) and Survivin-2B (p=0.027) was observed, while no change was found for Survivin-deltaEx3 and Survivin-3B variants. These results demonstrate for the first time that Survivin variants are differentially expressed in breast cancer according to tumour progression and treatment and suggest that Survivin-3B might act as an antiapoptotic factor in this lesion, with its expression regulated by p53.
Vegran
Frédérique
F
Laboratory of Molecular Genetic INSERM U-517, Dijon, France.
Boidot
Romain
R
Oudin
Claire
C
Riedinger
Jean-Marc
JM
Lizard-Nacol
Sarab
S
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C107489:BIRC5 protein, human; D018076:DNA, Complementary; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D012313:RNA