Haase C, Bergmann R, Oswald J, Zips D, Pietzsch J
Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Research Center Rossendorf, POB 51 01 19, 01314 Dresden, Germany.
Anticancer Res. 2006 Sep-Oct;26(5A):3527-33.
Peptide receptors seem to be good markers for receptor targeting because of their overexpression in human cancer. Understanding the role of receptors and their cognate ligands, they are currently used for both diagnosis and therapy. Candidates playing a key role in tumor biology are the neurotensin receptors (NTR). The expression of NTR in HT-29 cells (human colon adenocarcinoma cell line), FaDu cells (human squamous cell carcinoma cell line) and in corresponding tumor xenografts on nude mice, was investigated.
Quantitative RT-PCR of the three receptor subtypes was carried out to study mRNA expression. Receptor protein expression was analyzed by immunohistochemistry with specific antibodies for the three known neurotensin receptors NTR1, NTR2 and NTR3.
Analysis of receptor mRNA revealed a strong expression of NTR3 and a weak expression of NTR1 and NTR2 in cultured cells and xenografts. Examining the protein levels, a strong signal for NTR1 was detected in tumor cells and xenografts and only a weak signal was detected for NTR3.
Since the receptor protein is targeted in vivo, the enhanced protein expression of NTR1 in xenografts could be a useful tool for molecular targeting with radioligands and for further characterization of the carcinogenic process.
肽受体因其在人类癌症中的过表达,似乎是受体靶向治疗的良好标志物。了解受体及其同源配体的作用后,它们目前被用于诊断和治疗。在肿瘤生物学中起关键作用的候选者是神经降压素受体(NTR)。研究了NTR在HT-29细胞(人结肠腺癌细胞系)、FaDu细胞(人鳞状细胞癌细胞系)以及相应的裸鼠肿瘤异种移植模型中的表达情况。
对三种受体亚型进行定量逆转录聚合酶链反应(RT-PCR)以研究mRNA表达。通过免疫组织化学,使用针对三种已知神经降压素受体NTR1、NTR2和NTR3的特异性抗体分析受体蛋白表达。
受体mRNA分析显示,在培养细胞和异种移植模型中,NTR3表达强烈,NTR1和NTR2表达较弱。检测蛋白水平时,在肿瘤细胞和异种移植模型中检测到NTR1的强信号,而NTR3仅检测到弱信号。
由于受体蛋白是体内靶向的,异种移植模型中NTR1蛋白表达增强可能是用放射性配体进行分子靶向以及进一步表征致癌过程的有用工具。