Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer.
Skp2 is an F-box protein involved in the ubiquitination and subsequent degradation of the cyclin-dependent kinase (Cdk) inhibitor p27. Skp2 has been reported to be overexpressed in a variety of cancer types and to correlate with poor prognosis. We have identified a novel isoform of Skp2 we named Skp2B, which differs from Skp2 only in the C-terminal domain and unlike Skp2 localizes to the cytoplasm. Here, we describe the relative expression of both Skp2 and Skp2B in breast cancer cell lines and in primary breast cancers using quantitative real time RT-PCR. We show that Skp2B mRNA is expressed 10-fold less than Skp2 mRNA in the immortalized but non-transformed breast cell line, 184B5. However, Skp2B is overexpressed as frequently as Skp2, and to higher levels than Skp2 in breast cancer cell lines and primary cancers. Further, we show that cytoplasmic staining is frequent in primary breast cancers. In addition, we found that xenografts expressing Skp2B grow faster than xenografts expressing low levels of Skp2B, and that this effect is independent of p27 degradation. These findings therefore suggest that Skp2B overexpression is also observed in breast cancers and identify Skp2B as a putative oncogene.
Radke
Susanne
S
Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA.
Pirkmaier
Andreja
A
Germain
Doris
D
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044783:F-Box Proteins / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009857:Oncogenes; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014452:Ubiquitins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D020033:Protein Isoforms; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D050760:Cyclin-Dependent Kinase Inhibitor p27