Artikel
AKAP12 / Gravin – a candidate tumor suppressor gene is down regulated in breast cancer
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Autoren
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Michaela Blankenburg
- Max Delbrück Center for Molecular Medicine, Department of Tumor Genetics, Berlin, Deutschland
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Wera Hofmann
- Max Delbrück Center for Molecular Medicine, Department of Tumor Genetics, Berlin
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Susanne Seitz
- Max Delbrück Center for Molecular Medicine, Department of Tumor Genetics, Berlin
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Jana Strissel
- Max Delbrück Center for Molecular Medicine, Department of Tumor Genetics, Berlin
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Bernd Hinzmann
- Signature Diagnostics AG, Potsdam
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Siegfried Scherneck
- Max Delbrück Center for Molecular Medicine, Department of Tumor Genetics, Berlin
| Veröffentlicht: | 20. März 2006 |
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Gliederung
Text
We identified AKAP12 (A-kinase anchoring protein) as a candidate tumor suppressor gene in breast cancer. AKAP12, also known as gravin, has been mapped on chromosome 6q24-25.2, a hot spot region of loss of heterozygosity (LOH) in breast cancer. AKAP12 is a scaffold protein involved in signalling pathways. Significant down regulation of AKAP12 expression in breast tumors was shown by cancer profiling and chip array experiments, northern blot analysis and semiquantitative RT-PCR. To correlate expression of AKAP12 mRNA and LOH at the AKAP12 locus in primary breast tumors we analysed tumor probes in comparison to matched normal genomic DNA by sequencing of different SNPs and by amplification of the gene internal marker D6S476. To evaluate whether down regulation of AKAP12 expression is due to aberrant methylation we performed methylation-specific PCR and 5’-Aza-dC treatment. Based on the expression data we investigated the effect of AKAP12 on breast cancer cell growth by transient and stabile transfection into a breast cancer cell line. Data as to the gene expression and ability of the gene to retard tumor cell growth will be presented with respect to their relevance in tumorigenesis of breast cancer.
