The expression of BIRC5 is correlated with loss of specific chromosomal regions in breast carcinomas.
Expression of BIRC5 (survivin), a member of the inhibitor of apoptosis protein (IAP) family, is elevated in fetal tissues and in various human cancers. Mechanisms up-regulating BIRC5 in cancer are poorly understood. Here, we show that overexpression of BIRC5 induces a high proliferation level in MCF-7 breast tumor cells. In a population of 191 breast carcinomas, BIRC5 expression is not affected by BIRC5 promoter polymorphism at -31, or BIRC5 gene copy number. However, a significant correlation was found between expression of demethylase (dMTase) and expression of BIRC5. In addition, among 13 chromosomal regions tested for allelic loss [loss of heterozygosity (LOH)], two regions close to D3S1478 and D6S264 were related to BIRC5 expression. In tumors with LOH at D3S1478 and/or D6S264, BIRC5 expression was significantly increased. These regions have been suggested to harbor tumor suppressor genes and/or common fragile sites that may play a role in increasing genetic instability. These results suggest that genes located near D3S1478 and D6S264 might work by inhibiting, directly or indirectly, BIRC5 expression and thus their loss leads to its up-regulation. In addition, BIRC5 expression may induce breast tumor proliferation by promoting genetic instability. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
Boidot
Romain
R
Molecular Genetics Laboratory, Centre Georges-François Leclerc, IFR Santé-STIC, Dijon, France.
Vegran
Frédérique
F
Jacob
Delphine
D
Chevrier
Sandy
S
Gangneux
Nicolas
N
Taboureau
Johann
J
Oudin
Claire
C
Rainville
Vinciane
V
Mercier
Liliane
L
Lizard-Nacol
Sarab
S
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D049109:Cell Proliferation; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014162:Transfection; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin