The tumorigenicity diversification in human embryonic kidney 293 cell line cultured in vitro

Shen, Chao; Gu, Meijia; Song, Chao; Miao, Lei; Liu, Hu; Liang, Dan; Zheng, Chengchao

doi:10.1016/j.biologicals.2008.02.002

Cited by 50 publications

(45 citation statements)

References 14 publications

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“…The cell line, 293, may exhibit tumorigenicity diversification in nude mice because of multiple passages. 33 This property makes it possible for this cell line to be used as a model to express cancer-associated genes for the purpose of oncogenic potential or anti-tumor studies. 34,35 In this study, EBV genome infection in EBV-negative 293 cells resulted in obvious increase of cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

Tang

et al. 2010

Laboratory Investigation

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Epstein-Barr virus (EBV) is closely associated with several malignancies, including nasopharyngeal carcinoma. To investigate the EBV activity in tumor development, we tried to establish a malignant model of EBV-infected cells in nude mice. On the basis of the Maxi-EBV system, a human embryonic kidney epithelial cell line (293) with a low malignant potential was used for a stable EBV genome infection. The derived cell line, termed 293-EBV, exhibited obvious morphological transformation and significantly increased growth ability, with the cell cycle redistributed. The clonability and tumorigenicity were also substantially accelerated. In 293-EBV cells, the expression level of the transcription factor NF-kB and JNK2 were upregulated. The result suggested that latent membrane protein 1 (LMP1) was an important viral protein responsible for the enhanced malignant potential. Matured and budding virus particles were observed in tumor tissues, confirming the spontaneous reactivation of EBV from latent genome to lytic cycle at the site of tumor development. Primary culture of tumor tissues showed two patterns about the EBV maintenance or not in newly grown cells, and this was dependent on the thickness of the planted tissues. Moreover, the tumor cells lost EBV genome easily when subcultured at low density. Our findings revealed the cell-to-cell contact mechanism, which was required for the EBV maintenance in the tumor cells during the expansion of EBV-infected cells. This mechanism might give an explanation to the phenomenon that EBV genome in epithelial tumor cells becomes easily lost during subculture in vitro. Our results provided further evidence of a function for EBV in the etiology of tumor development.

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Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

Tang

et al. 2010

Laboratory Investigation

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“…Next, we performed softagar colony formation assays to assess whether miR-185 inhibits anchorage-independent growth. For our in vitro and in vivo tumorigenicity assays, we used miR-185 stably expressing HEK-293 cells passaged over 52 times, which are reported to be highly tumorigenic and cause tumor growth in immunocompromised mice (Shen et al, 2008). miR-185 stably overexpressing cells expectedly showed significantly lower Six1 levels (Supplementary Figure S3) and exhibited drastically reduced colony-forming capacity (colony number, size and nutrient consumption) when compared with vector control, suggesting a potential tumor suppressor-like activity (Figure 3a and Supplementary Figure S4).…”

Section: Mir-185 Targets Thementioning

confidence: 99%

MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers

et al. 2010

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Homeobox genes encode transcription factors that are essential for normal development and are often dysregulated in cancers. The molecular mechanisms that cause their misregulation in cancers are largely unknown. In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role during development, is frequently deregulated in several poor outcome, aggressive, metastatic adult human cancers, including breast cancer, ovarian cancer, hepatocellular carcinoma and pediatric malignancies such as rhabdomyosarcoma and Wilms' tumor. Our results reveal that miRNA-185 translationally represses Six1 by binding to its 3 0 -untranslated region. Analyses of ovarian cancers, pediatric renal tumors and multiple breast cancer cell lines showed decreased miR-185 expression, paralleling an increase in Six1 levels. Further investigation revealed that miR-185 impedes anchorage-independent growth and cell migration, in addition to suppressing tumor growth in vivo, implicating it to be a potent tumor suppressor. Our results indicate that miR-185 mediates its tumor suppressor function by regulating cell-cycle proteins and Six1 transcriptional targets c-myc and cyclin A1. Furthermore, we show that miR-185 sensitizes Six1-overexpressing resistant cancer cells to apoptosis in general and tumor necrosis factor-related apoptosisinducing ligand (TRAIL)-mediated apoptosis in particular. Together, our findings suggest that the altered expression of the novel tumor suppressor miR-185 may be one of the central events that leads to dysregulation of oncogenic protein Six1 in human cancers.

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“…Other studies have also noted that HEK 293 cells exhibit particularly low tumorigenicity. Shen et al (24) demonstrated that HEK 293 cell tumorigenicity increased with increasing passage number, and finally reached 100% when the passage number was >65; however, the original isolates of the cells did not form tumors at all in nude mice. In the present study, an outgrowth of tumors was detected in the absence of doxycycline in 5 cases (63%).…”

Section: Discussionmentioning

confidence: 99%

Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells

2016

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Fibroblast growth factor receptor-like 1 (FGFRL1) is a transmembrane receptor that interacts with heparin and FGF ligands. In contrast to the classical FGF receptors, FGFR1 to FGFR4, it does not appear to affect cell growth and proliferation. In the present study, an inducible gene expression system was utilized in combination with a xenograft tumor model to investigate the effects of FGFRL1 on cell adhesion and tumor formation. It was determined that recombinant FGFRL1 promotes the adhesion of HEK 293 Tet-On® cells in vitro. Moreover, when such cells are induced to express FGFRL1ΔC they aggregate into huge clusters. If injected into nude mice, the cells form large tumors. Notably, this tumor growth is completely inhibited when the expression of FGFRL1 is induced. The forced expression of FGFRL1 in the tumor tissue may restore contact inhibition, thereby preventing growth of the cells in nude mice. The results of the present study demonstrate that FGFRL1 acts as a tumor suppressor similar to numerous other cell adhesion proteins. It is therefore likely that FGFRL1 functions as a regular cell-cell adhesion protein.

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The tumorigenicity diversification in human embryonic kidney 293 cell line cultured in vitro

Cited by 50 publications

References 14 publications

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

Epstein–Barr virus facilitates the malignant potential of immortalized epithelial cells: from latent genome to viral production and maintenance

MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers

Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells

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