Systematic characterisation ofGABRPexpression in sporadic breast cancer and normal breast tissue


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Abstract

TheGABRPgene has been previously identified byin silicoanalysis of four million ESTs as a candidate gene differentially expressed in breast cancer.GABRPis located on chromosome 5q34 and it encodes the π-subunit of the γ-aminobutyric acid (GABA) receptor, a transmembrane protein expressed in the brain and several nonneuronal tissues. Using cDNA dot blot hybridisation (cancer profiling array), quantitative RT-PCR and non-radioisotopicin situhybridisation (ISH), we have analysedGABRPexpression in breast cancer and normal breast tissues as well as in nontumorigenic and tumorigenic breast cell lines. Analysis of the cancer profiling array revealed a more than 2-fold downregulation ofGABRP(p< 0.001) in 76% of primary breast carcinomas (n= 50) compared to corresponding normal tissues. Quantitative RT-PCR in a panel of 23 normal human tissues showed that theGABRPexpression level was most abundant in the normal breast tissues compared to other human tissues.GABRPdownregulation in breast cancer was confirmed by quantitative RT-PCR in cryopreserved breast tumour and normal breast tissue specimens (n= 22), in archival formalin-fixed, paraffin-embedded tissue specimens (n= 32), as well as in breast cancer cell lines (n= 8). Furthermore, a significant downregulation ofGABRPwas noted in large (pT3-pT4) (p= 0.044) primary breast tumours. Non-radioisotopic ISH showed strongGABRPexpression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest thatGABRPis progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.

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