Variation of Keratin 7 Expression and Other Phenotypic Characteristics of Independent Isolates of Cadmium Transformed Human Urothelial Cells (UROtsa)

Variation of Keratin 7 Expression and Other Phenotypic Characteristics of Independent Isolates of Cadmium Transformed Human Urothelial Cells (UROtsa)
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DOI:
10.1021/tx900346q
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发表时间:
2010-02-01
影响因子:
4.1
通讯作者:
Sens, Donald. A.
Sens, Donald. A.
中科院分区:
医学3区
文献类型:
--
作者:
Somji, Seema;Zhou, Xu Dong;Sens, Donald. A.

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本实验室已证明,镉(Cd 2+)转化的人尿路上皮细胞系(UROtsa)产生类似于人移行细胞癌(TCC)的皮下肿瘤异种移植物。在本研究中,额外的Cd2+转化细胞系被分离,以确定是否独立暴露的细胞系Cd2+将导致恶性转化的细胞系具有相似的表型特性。7个独立的分离株,并评估其倍增时间,形态,异源移植皮下和裸鼠腹腔的能力,角蛋白7的表达。7个细胞系均显示上皮形态,无鳞状分化的证据。倍增时间是可变的分离株之间,显着减少或类似的亲本细胞。所有7个分离株均能形成具有TCC形态的皮下肿瘤异种移植物,并且所有异种移植物均显示移行细胞的鳞状分化区域。鳞状分化的程度各不相同的菌株。与皮下肿瘤形成相反,只有1个分离的Cd2+转化细胞(UTCd#1)能够有效地定殖在腹膜腔内的多个部位。角蛋白7的表达分析表明,对于从7个细胞系产生的皮下异种移植物,角蛋白7的表达与鳞状分化无关。角蛋白7在7个细胞系中的6个及其皮下肿瘤异种移植物中表达。角蛋白7在能够在腹膜腔内形成肿瘤的细胞系中不表达。这些结果表明,个别分离的Cd 2+转化细胞既有相似之处,又有不同的表型。
This laboratory has shown that a human Urothelial cell line (UROtsa) transformed by cadmium (Cd2+) produced subcutaneous tumor heterotransplants that resemble human transitional cell carcinoma (TCC). In the present study, additional Cd2+ transformed cell lines were isolated to determine if independent exposures of the cell line to Cd2+ would result in malignantly transformed cell lines possessing similar phenotypic properties. Seven independent isolates were isolated and assessed for their doubling times, morphology, ability to heterotransplant Subcutaneously and in the peritoneal cavity of nude mice, and for the expression of keratin 7. The 7 cell lines all displayed an epithelial morphology with no evidence of squamous differentiation. Doubling times were variable among the isolates, being significantly reduced or similar to those of the parental cells. All 7 isolates were able to form subcutaneous tumor heterotransplants with a TCC morphology, and all heterotransplants displayed areas of squamous differentiation of the transitional cells. The degree of squamous differentiation varied among the isolates. In contrast to subcutaneous tumor formation, only 1 isolate of the Cd2+ transformed cells (UTCd#1) was able to effectively colonize multiple sites within the peritoneal cavity. An analysis of keratin 7 expression showed no correlation with squamous differentiation For the subcutaneous heterotransplants generated from the 7 cell lines. Keratin 7 was expressed in 6 of the 7 cell lines and their subcutaneous tumor heterotransplants. Keratin 7 was not expressed in the cell line that was able to form tumors within the peritoneal cavity. These results show that individual isolates of Cd2+ transformed cells have both similarities and differences in their phenotype.