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Expression of MUCI splice variants correlates with invasive growth of breast cancer cell lines
Authors:Schmid Bernd C  Buluwela Laki  Liu QiuYan  Fasching Barbara  Tong Dan  Stimpfl Margit  Andreas Obermair  Leodolter Sepp  Zeillinger Robert
Affiliation:(1) Molecular Oncology Group, Division of Gynecology, Department of Obstetrics and Gynecology, University of Vienna, Vienna, Austria;(2) Division of Medicine, Cancer Cell Biology Section, Imperial College School of Medicine, Hammersmith Campus, London, UK;(3) Ludwig-Boltzmann Institute for Gynaecological Oncology and Reproductive Medicine, Vienna, Austria
Abstract:On the basis of alternative splicing the human breast cancer associated MUCI gene codes for different protein products. MUCI splice variants A and B have been shown to be determined by a single A/G nucleotide polymorphism (SNP) in exon 2 of the MUCI gene. We now describe two new splice variants C and D and show by that in human breast cancer cell lines there is selective co-expression of these variants, namely co-expression of variants A and D. We have found that the expression of variants C and D is also determined by the same SNP in exon 2. Since the overexpression of MUCI proteins has been associated with increased invasive behavior of cancer cell lines, we quantitatively determined the mRNA expression levels of the splice variants A, B, C, and D in breast cancer cell lines and correlated them with the in vitro invasiveness of these cell lines. We revealed a significant correlation between the lack of MUCI splice variants B and C and the invasiveness of the cell lines tested. Furthermore, we showed that concomitant expression of variants A and D is associated with a GG in the genotype. These findings suggest that the invasive behavior of breast cell lines may depend on different expression patterns of the MUCI gene determined by a genetic polymorphism.
Keywords:breast cancer  invasiveness  MUCI  real-time RT-PCR  splice variants
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