Reassessment of Id1 protein expression in human mammary, prostate, and bladder cancers using a monospecific rabbit monoclonal anti-Id1 antibody
Reassessment of Id1 protein expression in human mammary, prostate, and bladder cancers using a monospecific rabbit monoclonal anti-Id1 antibody
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DOI：
10.1158/0008-5472.can-06-2643
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发表时间：
2006-11-15
期刊：
影响因子：
11.2
通讯作者：
Benezra, Robert
中科院分区：
文献类型：
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作者：
Perk, Jonathan;Gil-Bazo, Ignacio;Benezra, Robert
Id蛋白是一类螺旋-环-螺旋转录因子的显性负性拮抗剂，并已被证明在多种生物体中控制多种细胞类型的分化。虽然Id 1在肿瘤内皮细胞中的重要性已得到充分证实，但Id 1蛋白在人类癌细胞中的表达和作用仍存在争议。为了探讨这个问题，我们开发了一种高度特异性的兔抗Id 1单克隆抗体，以评估其在人类乳腺癌，前列腺癌和膀胱癌中的表达。我们的研究结果表明，在常见类型的人乳腺癌，Id 1蛋白只在内皮细胞中表达。有趣的是，我们检测到10的45例低分化和高度侵袭性癌化生形态的肿瘤细胞中的Id 1蛋白的核表达。同样，30例前列腺癌样本中只有1例显示Id 1阳性肿瘤细胞，而几乎所有样本中，内皮细胞均显示Id 1高表达。有趣的是，虽然正常前列腺不显示任何Id 1蛋白表达，但良性前列腺的基底层细胞在肿瘤附近表达高水平的Id 1蛋白。与通常类型的乳腺癌和前列腺癌中缺乏Id 1表达相反，大多数膀胱移行细胞肿瘤在肿瘤和内皮细胞中显示Id 1蛋白表达。这些结果表明，进一步细化Id 1在各种肿瘤类型的表达模式将是必要的，以确定和研究Id 1在人类肿瘤过程中发挥的功能作用。
Id proteins are a class of dominant-negative antagonists of helix-loop-helix transcription factors and have been shown to control differentiation of a variety of cell types in diverse organisms. Although the importance of Id1 in tumor endothelial cells is well established, the expression and role of the Id1 protein in human cancer cells is controversial. To explore this issue, we developed and characterized a highly specific rabbit monoclonal antibody against Id1 to assess its expression in human breast, prostate, and bladder malignancies. Our results show that in usual types of human mammary carcinomas, the Id1 protein is expressed exclusively in the endothelium. Interestingly, we detected nuclear expression of the Id1 protein in the tumor cells in 10 of 45 cases of poorly differentiated and highly aggressive carcinoma with metaplastic morphology. Similarly, only 1 of 30 prostate cancer samples showed Id1-positive tumor cells, whereas in almost all, endothelial cells showed high Id1 expression. Intriguingly, whereas normal prostate glands do not show any Id1 protein expression, basal layer cells of benign prostate glands in proximity to tumors expressed high levels of the Id1 protein. In contrast to the lack of Id1 expression in the usual types of mammary and prostate cancers, the majority of transitional cell bladder tumors showed Id1 protein expression in both tumor and endothelial cells. These results suggest that further refinement of Id1 expression patterns in a variety of tumor types will be necessary to identify and study the functional roles played by Id1 in human neoplastic processes.