Keratin 6 expression correlates to areas of squamous differentiation in multiple independent isolates of As(+3)-induced bladder cancer.

Keratin 6 expression correlates to areas of squamous differentiation in multiple independent isolates of As(+3)-induced bladder cancer.
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DOI:
10.1002/jat.1513
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发表时间:
2010-07
影响因子:
3.3
通讯作者:
Somji, Seema
Somji, Seema
中科院分区:
医学4区
文献类型:
--
作者:
Cao, Ling;Zhou, Xu Dong;Sens, Mary Ann;Garrett, Scott H.;Zheng, Yun;Dunlevy, Jane R.;Sens, Donald A.;Somji, Seema

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该实验室已表明,砷(As+3)暴露可导致UROtsa人尿路上皮细胞系的恶性转化。该单一分离株形成皮下肿瘤,其组织学类似于人尿路上皮细胞癌。肿瘤还显示了尿路上皮细胞的鳞状分化区域,这是一种罕见但已知的人类膀胱癌成分。在本研究中,五个额外的独立的分离的As+3转化的尿路上皮细胞被分离出来,每个被证明产生皮下尿路上皮细胞肿瘤的组织学特征非常相似,在最初的报告中所描述的。当评估6个独立分离株在腹膜腔内形成肿瘤的能力时,证明了它们存在潜在的表型差异。结果表明,2株可形成数百个小的腹膜肿瘤结节,1株可形成中等数量的肿瘤结节,3株不形成或仅形成一个肿瘤结节。腹膜肿瘤的特征还在于尿路上皮细胞的鳞状分化程度,虽然可以发现鳞状分化区域,但与皮下肿瘤相比,这种分化大大减少。角蛋白6的免疫染色作为一个潜在的标志物进行了测试,恶性尿路上皮细胞已经历鳞状分化。角蛋白6显示仅对具有一些鳞状分化证据的细胞一致染色。角蛋白16显示遵循角蛋白6的染色模式。分离物和肿瘤异源移植物均检测角蛋白6、16和17 mRNA和蛋白表达。
This laboratory has shown that arsenite (As+3) exposure can cause the malignant transformation of the UROtsa human urothelial cell line. This single isolate formed subcutaneous tumors with a histology similar to human urothelial cell carcinoma. The tumors also displayed areas of squamous differentiation of the urothelial cells, an infrequent, but known component of human bladder cancer. In the present study, five additional independent isolates of As+3 -transformed urothelial cells were isolated and each were shown to produce subcutaneous urothelial cell tumors with a characteristic histology very similar to those described in the initial report. That there were underlying phenotypic differences in the 6 independent isolates was demonstrated when they were assessed for their ability to form tumors within the peritoneal cavity. It was shown that two isolates could form hundreds of small peritoneal tumor nodules, one isolate a moderate number of tumor nodules, and three isolates no or only one tumor nodule. The peritoneal tumors were also characterized for their degree of squamous differentiation of the urothelial cells and, while areas of squamous differentiation could be found, such differentiation was substantially reduced compared to subcutaneous tumors. Immunostaining for keratin 6 was tested as a potential marker for malignant urothelial cells that had undergone squamous differentiation. Keratin 6 was shown to consistently stain only cells having some evidence of squamous differentiation. Keratin 16 was shown to follow the staining pattern of keratin 6. The isolates and tumor heterotransplants were all examined for keratin 6, 16 and 17 mRNA and protein expression.
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AS和CD通过AS和CD转化人尿路上皮细胞(UROTSA)会诱导角蛋白6a的表达。
DOI: 10.1289/ehp.10279
发表时间: 2008-04
影响因子: 10.4
作者:
Somji, Seema;Bathula, Chandra S.;Zhou, Xu Dong;Sens, Mary Ann;Sens, Donald A.;Garrett, Scott H.
通讯作者: Garrett, Scott H.