The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity.

The LIM-only protein, LMO4, and the LIM domain-binding protein, LDB1, expression in squamous cell carcinomas of the oral cavity.
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LIM蛋白LMO4和LIM结构域结合蛋白LDB1在口腔鳞状细胞癌中的表达。

DOI:
10.1038/sj.bjc.6600952
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发表时间:
2003-05-19
影响因子:
8.8
通讯作者:
Imai, K
Imai, K
中科院分区:
医学1区
文献类型:
--
作者:
Mizunuma, H;Miyazawa, J;Sanada, K;Imai, K

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在肿瘤的发展过程中,癌细胞可以失去其上皮细胞的特征并去分化为成纤维细胞样细胞。低聚转录复合物的异常表达有助于癌症的进展。尽管启动进展的单个转录因子尚不清楚,但LIM-only蛋白(LMO)和lim结构域结合蛋白(LDB)负向调节乳腺癌细胞分化。本研究探讨了LMO4和LDB在口腔鳞状细胞癌中的表达。lmo4mrna在6个癌组织中的4个和12个细胞系中的8个中扩增,LDB1在3个癌组织和11个细胞系中扩增。免疫沉淀研究显示,LMO4和LDB1在癌细胞的核环境中相互作用,表明存在LMO4-LDB1介导的转录复合物。LMO4和LDB1蛋白均优先定位于侵袭前沿的癌细胞细胞核,低分化癌组织的免疫反应性增强(P<0.01)。与肿瘤原发部位相比,转移至颈部淋巴结的癌细胞免疫反应性增高(P<0.05)。这些数据表明,LMO4-LDB1复合物可能通过口腔鳞癌细胞的去分化参与了癌的进展。
Carcinoma cells can lose their epithelial cell characteristics and dedifferentiate into a fibroblast-like cell during progression of a neoplasm. Aberrant expression of oligomeric transcriptional complexes contributes to progression of carcinomas. Although individual transcription factors initiating progression remain unknown, LIM-only protein (LMO) and LIM-domain binding protein (LDB) negatively regulate breast carcinoma cell differentiation. In this study, we investigated the expression of LMO4 and LDB in squamous cell carcinomas of the oral cavity. LMO4 mRNA was amplified in four of six carcinoma tissues and eight of 12 carcinoma cell lines, and LDB1 in three carcinoma tissues and 11 cell lines examined. Immunoprecipitation studies revealed that LMO4 and LDB1 interact with each other in the nuclear milieu of the carcinoma cells indicating the presence of an LMO4-LDB1-mediated transcription complex. Both LMO4 and LDB1 proteins were preferentially localised in the nuclei of carcinoma cells at the invasive front and the immunoreactivity was increased in less-differentiated carcinoma tissues (P<0.01). Carcinoma cells metastasised to the cervical lymph nodes with increased immunoreactivity compared to the primary site of neoplasm (P<0.05). These data suggest that the LMO4–LDB1 complexes may be involved in carcinoma progression possibly through dedifferentiation of squamous carcinoma cells of the oral cavity.