Kebebew E, Treseler P A, Duh Q Y, Clark O H
Department of Surgery, University of California, San Francisco, 91434-0470, USA.
Surgery. 2000 Dec;128(6):952-7. doi: 10.1067/msy.2000.111082.
The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis.
The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis.
Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression.
Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation.
Id-1螺旋-环-螺旋蛋白可抑制分化并增强细胞增殖。它是细胞周期进展所必需的。Id-1基因在多种肿瘤来源的细胞系中高度表达。在有丝分裂原刺激后其表达增加，并且在一些人类肿瘤中过度表达。因此，我们推测Id-1基因可能在甲状腺髓样癌的发生中起作用。
通过Id-1免疫组织化学法测定Id-1蛋白在人甲状腺髓样癌（MTC）及相应正常甲状腺组织中的表达。在人MTC细胞系（TT）中，通过Northern印迹分析确定生长刺激和再分化对Id-1表达的影响。
9例MTC样本（6例散发性、2例家族性和1例MEN 2A）的Id-1免疫染色强度为中度至强阳性。然而，在相应的正常甲状腺组织中未检测到或染色较弱。基于阳性细胞百分比和免疫染色强度，与相应正常甲状腺组织相比，MTC中Id-1蛋白明显过度表达（P = 0.002）。在TT细胞系中，血清生长刺激后Id-1信使核糖核酸（mRNA）表达增加4倍。佛波酯（可诱导TT细胞系再分化）下调Id-1 mRNA表达。
Id-1在MTC中过度表达。Id-1基因可能在MTC分化和增殖的调节中起作用。
