Transformation of human urothelial cells (UROtsa) by as and cd induces the expression of keratin 6a.
Transformation of human urothelial cells (UROtsa) by as and cd induces the expression of keratin 6a.
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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
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发表时间：
2008-04
影响因子：
10.4
通讯作者：
Garrett, Scott H.
中科院分区：
文献类型：
--
作者：
Somji, Seema;Bathula, Chandra S.;Zhou, Xu Dong;Sens, Mary Ann;Sens, Donald A.;Garrett, Scott H.
镉和亚砷酸盐可直接恶性转化URotsa细胞系。从这些转化的细胞产生的肿瘤异种移植具有与人类膀胱癌一致的组织学特征。先前对亲本细胞和转化细胞总RNA的微阵列分析表明，角蛋白6a在细胞转化过程中过度表达。我们的目标是验证角蛋白6a在CD2+和As3+转化的UROtsa细胞、相应的肿瘤异种移植和人膀胱癌活检标本中的过度表达，并评估哪些因素可能参与角蛋白6a的过度表达。用实时定量聚合酶链式反应、Western印迹分析和免疫组织化学方法检测其表达。我们利用细胞培养上清液中潜在生长因子的添加和删除的影响来评估角蛋白6a过表达的可能途径。Cd~(2+)和As~(3+)转化细胞在含血清培养液中生长，与在含血清培养液中生长的URotsa细胞相比，肿瘤异种移植瘤细胞角蛋白6a基因和蛋白的表达水平均较高。异种移植瘤细胞角蛋白6a免疫组织化学染色显示瘤细胞局灶性染色，定位于细胞质。在一些但不是所有高级别膀胱癌的档案患者样本中也发现了角蛋白6a的局部免疫染色，证实了该结果与人类膀胱癌的关系。对生长因子缺失和添加的研究表明，角蛋白6a的表达水平受胰岛素和表皮生长因子(EGF)的共同调节。相反，生长因子对转化的UROtsa细胞中角蛋白6a表达水平的升高没有影响。我们目前的研究表明，角蛋白6a的表达可能是具有激活的EGF和/或胰岛素生长因子途径的恶性尿路上皮细胞的生物标志物。
Cadmium and arsenite can directly and malignantly transform the UROtsa cell line. The tumor heterotransplants produced from these transformed cells have histologic features consistent with human bladder cancer. Previous microarray analysis of total RNA from the parental and transformed cells suggested that keratin 6a was overexpressed as a result of cell transformation. Our goals were to verify overexpression of keratin 6a in Cd2+- and As3+-transformed UROtsa cells, the corresponding tumor heterotransplants, and human bladder cancer biopsy specimens and to assess what factors may be involved in keratin 6a overexpression. Expression was assessed with real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. We used the effect of addition and deletion of potential growth factors in the cell culture growth medium to assess possible pathways used in keratin 6a overexpression. Cd2+- and As3+-transformed cells grown in serum-containing growth medium, as well as the derived tumor heterotransplants, overexpressed keratin 6a mRNA and protein compared with UROtsa cells grown in serum-containing growth medium. Immunostaining of keratin 6a in tumor heterotransplants showed focal staining of the tumor cells that was localized to the cytoplasm. Focal immunostaining of keratin 6a was also found in some but not all archival patient specimens of high-grade bladder cancer, confirming translation of the results to human bladder cancer. Studies on growth factor deletion and addition indicated that the level of keratin 6a expression was regulated by the presence of both insulin and epidermal growth factor (EGF). In contrast, growth factors had no effect on the elevated levels of keratin 6a expression found in transformed UROtsa cells. Our present studies suggest that keratin 6a expression may be a biomarker for malignant urothelial cells that possess an activated EGF and or insulin growth factor pathway.
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影响因子：
7.5
作者：
Chu, PG;Wu, E;Weiss, LM
通讯作者：
Weiss, LM
DOI：
10.1083/jcb.200603161
发表时间：
2006-07-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Schweizer J;Bowden PE;Coulombe PA;Langbein L;Lane EB;Magin TM;Maltais L;Omary MB;Parry DA;Rogers MA;Wright MW
通讯作者：
Wright MW
影响因子：
2.4
作者：
Maloney, ME
通讯作者：
Maloney, ME
影响因子：
4.8
作者：
Safer, JD;Crawford, TM;Holick, MF
通讯作者：
Holick, MF
影响因子：
2.7
作者：
Smiley, AK;Klingenberg, JM;Supp, DM
通讯作者：
Supp, DM