Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue
Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue
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DOI：
10.1002/ijc.21517
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发表时间：
2006-03-15
影响因子：
6.4
通讯作者：
Dahl, E
中科院分区：
文献类型：
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作者：
Zafrakas, M;Chorovicer, M;Dahl, E
GABRP基因先前已经通过计算机分析400万个EST被鉴定为在乳腺癌中差异表达的候选基因。GABRP位于染色体5 q34上，它编码γ-氨基丁酸（GABA）受体的pi亚基，γ-氨基丁酸受体是一种在脑和几种非神经组织中表达的跨膜蛋白。使用cDNA斑点杂交（癌症分析阵列），定量RT-PCR和非放射性同位素原位杂交（ISH），我们分析了GABRP在乳腺癌和正常乳腺组织以及在非致瘤性和致瘤性乳腺细胞系的表达。癌症谱阵列的分析显示，与相应的正常组织相比，76%的原发性乳腺癌（n = 50）中GABRP的下调超过2倍（p < 0.001）。在一组23个正常人体组织中的定量RT-PCR显示，与其他人体组织相比，GABRP在正常乳腺组织中的表达水平最丰富。在冷冻保存的乳腺肿瘤和正常乳腺组织标本（n = 22），存档福尔马林固定的石蜡包埋组织标本（n = 32），以及乳腺癌细胞系（n = 8）中，通过定量RT-PCR证实乳腺癌中GABRP下调。此外，在大的（pT 3-pT 4）（p = 0.044）原发性乳腺肿瘤中观察到GABRP的显著下调。非放射性同位素原位杂交显示GABRP在正常上皮和良性乳头状瘤乳腺细胞中有强表达，但在浸润性导管癌中未检测到信号。总之，这些数据表明GABRP随着肿瘤进展而逐渐下调，并且它可能用作乳腺癌的预后标志物。(c)2005 Wiley-Liss，Inc.
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-em bedded 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. (c) 2005 Wiley-Liss, Inc.