title: Apoptosis gene signature of Survivin and its splice variant expression in breast carcinoma.
abstract: Survivin, an anti-apoptotic protein, was described as strongly expressed in human cancers including breast cancer. However, little is known about the association between Survivin variants (Survivin-2B, Survivin-ΔEx3, Survivin-3B, and Survivin-2α) and the other apoptotic-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Human Apoptosis Gene Arrays were used to screen genes that could be associated with Survivin variants. Expression of the five transcripts was measured by RT-PCR in 135 breast carcinomas and Cox survival analysis was analyzed according to the patient outcome. Significant associations between Survivin transcripts and apoptotic genes were found. Interestingly, Survivin-3B variant showed major inverse correlations with pro-apoptotic genes. In addition, in vitro results indicated that overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/cyclophosphamide-induced apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of Survivin-3B expression had a shorter overall (P=0.030 and P=0.042 respectively), and disease-free (P=0.024 and P=0.009) survival. Our data suggest that Survivin-3B contributes to cell survival through the anti-apoptotic pathway and that its expression level could be an important factor in determining therapeutic strategies for breast carcinoma.
authors: Molecular Biology Laboratory, EA 4184, Centre Georges-François Leclerc, IFR Santé-STIC, 1 Rue du Professeur Marion, 21079 Dijon Cedex, France.
authors: Frédérique
authors: F
authors: Végran
authors: Romain
authors: R
authors: Boidot
authors: Franck
authors: F
authors: Bonnetain
authors: Muriel
authors: M
authors: Cadouot
authors: Sandy
authors: S
authors: Chevrier
authors: Sarab
authors: S
authors: Lizard-Nacol
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D015251:Epirubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil