title: Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue.
abstract: The GABRP gene has been previously identified by in silico analysis of four million ESTs as a candidate gene differentially expressed in breast cancer. GABRP is located on chromosome 5q34 and it encodes the pi-subunit of the gamma-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-radioisotopic in situ hybridisation (ISH), we have analysed GABRP expression 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 of GABRP (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 the GABRP expression level was most abundant in the normal breast tissues compared to other human tissues. GABRP downregulation 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 of GABRP was noted in large (pT3-pT4) (p = 0.044) primary breast tumours. Non-radioisotopic ISH showed strong GABRP expression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.
authors.affiliation: Institute of Pathology, University Hospital of the RWTH, Aachen, Germany.
authors.forename: Menelaos
authors.initials: M
authors.lastname: Zafrakas
authors.forename: Marina
authors.initials: M
authors.lastname: Chorovicer
authors.forename: Irima
authors.initials: I
authors.lastname: Klaman
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Peter-Johannes
authors.initials: PJ
authors.lastname: Wild
authors.forename: Uwe
authors.initials: U
authors.lastname: Heindrichs
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
mesh_terms: D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D021122:Protein Subunits / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C519780:GABRP protein, human; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A