Parafibromin expression is an independent prognostic factor for colorectal carcinomas
Parafibromin expression is an independent prognostic factor for colorectal carcinomas
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DOI：
10.1016/j.humpath.2010.10.024
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发表时间：
2011-08-01
期刊：
影响因子：
3.3
通讯作者：
Takano, Yasuo
中科院分区：
文献类型：
--
作者：
Zheng, Hua-chuan;Wei, Zheng-li;Takano, Yasuo
副纤维蛋白是由甲状旁腺素2编码的蛋白质，其表达下调参与甲状旁腺癌、乳腺癌和胃癌的发病机制。本研究旨在阐明副纤维蛋白在大肠癌发生、发展和预后中的作用。将副纤蛋白表达质粒转染DLD-1细胞，检测相关分子。通过免疫组化、原位杂交、Western印迹或逆转录聚合酶链反应检测结直肠样本中的副纤维蛋白表达。结果表明，parafibromin过表达可引起DLD-1细胞G1期阻滞，并促进其分化。p21、p27和细胞周期蛋白E高表达，而细胞周期蛋白D1信使RNA、磷酸化cdc 2和磷酸化cdc 25 c蛋白低表达。Parafibromin可通过与c-myc启动子结合抑制c-myc mRNA的表达。从结直肠非肿瘤性粘膜和腺瘤到结直肠癌，核旁纤维蛋白和旁纤维蛋白信使RNA的表达水平降低（P <0.05）。免疫组化结果显示，副纤维蛋白表达与肿瘤大小、浸润深度、淋巴结转移、临床病理分期和预后不良呈负相关（P <0.05）。结果表明，parafibromin过表达可抑制DLD-1细胞的细胞周期进程，促进DLD-1细胞分化。副纤维蛋白异常表达可能与结直肠癌的发生、生长、侵袭和转移有关，可作为结直肠癌患者预后良好的独立指标。(C)2011 Elsevier Inc. All rights reserved.
Parafibromin is a protein encoded by hyperparathyroidism 2, and its down-regulated expression is involved in the pathogenesis of parathyroid, breast, and gastric carcinomas. This study aimed to clarify the roles of parafibromin expression in tumorigenesis, progression, and prognosis of colorectal carcinomas. Parafibromin-expressing plasmid was transfected into DLD-1 cells with the phenotypes, and related molecules were examined. Parafibromin expression was examined in colorectal samples by immunohistochemistry, in situ hybridization, Western blot, or reverse transcription polymerase chain reaction. It was found that parafibromin overexpression could cause G1 arrest and enhance differentiation of DLD-1 cells. There was a high expression of p21, p27, and cyclin E, but low expression of cyclin D1 messenger RNA, phospho-cdc2, and phospho-cdc25c proteins. Parafibromin could inhibit c-myc, messenger RNA expression by binding to c-myc promoter. Expression levels of nuclear parafibromin and parafibromin messenger RNA were decreased from colorectal nonneoplastic mucosa and adenomas to carcinomas (P < .05). Immunohistochemically, parafibromin expression was inversely correlated with tumor size, depth of invasion, lymph node metastasis, clinicopathologic staging, and poor prognosis of carcinomas (P < .05). It was suggested that parafibromin overexpression might suppress cell cycle progression and promote differentiation of DLD-1 cells. Aberrant parafibromin expression possibly contributes to the pathogenesis, growth, invasion, and metastasis of colorectal carcinomas and could be regarded as an independent factor to indicate a favorable prognosis for patients with colorectal carcinomas. (C) 2011 Elsevier Inc. All rights reserved.