Mistaken Identity of Widely Used Esophageal Adenocarcinoma Cell Line TE-7

Department of Medicine, Stanford University, Palo Alto, California, United States
Cancer Research (Impact Factor: 9.33). 10/2007; 67(17):7996-8001. DOI: 10.1158/0008-5472.CAN-07-2064
Source: PubMed

ABSTRACT Cancer of the esophagus is the seventh leading cause of cancer death worldwide. Esophageal carcinoma cell lines are useful models to study the biological and genetic alterations in these tumors. An important prerequisite of cell line research is the authenticity of the used cell lines because the mistaken identity of a cell line may lead to invalid conclusions. Estimates indicate that up to 36% of the cell lines are of a different origin or species than supposed. The TE series, established in late 1970s and early 1980s by Nishihira et al. in Japan, is one of the first esophageal cancer cell line series that was used throughout the world. Fourteen TE cell lines were derived from human esophageal squamous cell carcinomas and one, TE-7, was derived from a primary esophageal adenocarcinoma. In numerous studies, this TE-7 cell line was used as a model for esophageal adenocarcinoma because it is one of the few esophageal adenocarcinoma cell lines existing. We investigated the authenticity of the esophageal adenocarcinoma cell line TE-7 by xenografting, short tandem repeat profiling, mutation analyses, and array-comparative genomic hybridization and showed that cell line TE-7 shared the same genotype as the esophageal squamous cell carcinoma cell lines TE-2, TE-3, TE-12, and TE-13. In addition, for more than a decade, independent TE-7 cultures from Japan, United States, United Kingdom, France, and the Netherlands had the same genotype. Examination of the TE-7 cell line xenograft revealed the histology of a squamous cell carcinoma. We conclude that the TE-7 cell line, used in several laboratories throughout the world, is not an adenocarcinoma, but a squamous cell carcinoma cell line. Furthermore, the cell lines TE-2, TE-3, TE-7, TE-12, and TE-13 should be regarded as one single squamous cell carcinoma cell line.

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Available from: H. Berna Beverloo, Sep 09, 2014
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    • "Human cell line TE7 derived from an oesophageal squamous cell carcinoma [24], kindly provided by Professor Wael El-Rifai (Vanderbilt University Medical Center, Nashville, USA), was maintained in DMEM with 10% foetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (100 μg/ml), and cultured in a humidified 5% CO2 atmosphere at 37°C. "
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    ABSTRACT: Cancer cells showing low apoptotic effects following oxidative stress-induced DNA damage are mainly affected by growth arrest. Thus, recent studies focus on improving anti-cancer therapies by increasing apoptosis sensitivity. We aimed at identifying a universal molecule as potential target to enhance oxidative stress-based anti-cancer therapy through a switch from cell cycle arrest to apoptosis. A cDNA microarray was performed with hydrogen peroxide-treated oesophageal squamous epithelial cancer cells TE7. This cell line showed checkpoint activation via p21(WAF1) , but low apoptotic response following DNA damage. The potential target molecule was chosen depended on the following demands: it should regulate DNA damage response, cell cycle and apoptosis. As the transcription factor ATF2 is implicated in all these processes, we focused on this protein. We investigated checkpoint activation via ATF2. Indeed, ATF2 knockdown revealed ATF2-triggered p21(WAF1) protein expression, suggesting p21(WAF1) transactivation through ATF2. Using chromatin immunoprecipitation (ChIP), we identified a hitherto unknown ATF2-binding sequence in the p21(WAF1) promoter. p-ATF2 was found to interact with p-c-Jun, creating the AP-1 complex. Moreover, ATF2 knockdown led to c-Jun downregulation. This suggests ATF2-driven induction of c-Jun expression, thereby enhancing ATF2 transcriptional activity via c-Jun-ATF2 heterodimerization. Notably, downregulation of ATF2 caused a switch from cell cycle arrest to reinforced apoptosis, presumably via p21(WAF1) downregulation, confirming the importance of ATF2 in the establishment of cell cycle arrest. 1-Chloro-2,4-dinitrobenzene also led to ATF2-dependent G2/M arrest, suggesting that this is a general feature induced by oxidative stress. As ATF2 knockdown also increased apoptosis, we propose ATF2 as a target for combined oxidative stress-based anti-cancer therapies.
    Journal of Cellular and Molecular Medicine 06/2013; 17(8). DOI:10.1111/jcmm.12071 · 4.01 Impact Factor
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    • "The human ESCC cell lines TE7 and TE15 [25] [26] were cultured at 37°C and 5% CO 2 in Dulbecco's modified Eagle's medium/F12 media (Life Technologies, Grand Island, NY) supplemented with 5% BSA (Life Technologies), 100 units/ml penicillin, and 100 μg/ml streptomycin (Life Technologies). For JNK inhibition, SP600125 (Enzo Life Sciences, Farmingdale, NY) was dissolved in DMSO, and cells were treated at 10 μM for 0, 4, 8, and 24 hours. "
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    ABSTRACT: Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.
    Neoplasia (New York, N.Y.) 05/2013; 15(5):472-80. DOI:10.1593/neo.122126 · 4.25 Impact Factor
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    • "More recently, cross-contamination of newly developed cell lines with older, established cell lines is becoming an increasingly recognized problem. Indeed, numerous misidentifications have been reported, some within the well-studied NCI-60 panel of cell lines (Lorenzi et al., 2009), in addition to cell lines thought to be of prostate (van Bokhoven et al., 2001a,b, 2003), breast (Rae et al., 2004, 2007; Liscovitch and Ravid, 2007), esophageal (Boonstra et al., 2007), adenoid cystic carcinoma (ACC; Phuchareon et al., 2009; Zhao et al., 2011), and head and neck squamous cell cancer (HNSCC) origin (Zhao et al., 2011). "
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    ABSTRACT: Thyroid cancer is the most common endocrine malignancy and the incidence is rising. Currently, there are no effective treatments for patients with advanced forms of thyroid cancer. Anaplastic thyroid represents the most severe form of the disease with 95% mortality at 6 months. It is therefore critical to better understand the mechanisms involved in thyroid cancer development and progression in order to develop more effective therapeutic strategies. Cell lines derived from thyroid tumors represent a critical tool to understand the oncogenic mechanisms driving thyroid cancer, as well as preclinical tools to study the efficacy of new therapies in vitro and in vivo. For thyroid cancer, the development of new therapies has been hampered by the lack of thyroid cancer cell lines in the widely used NCI-60 panel which has been used to screen over 100,000 anti-cancer drugs. In addition, the recent discovery that ~20 out of 40 existing thyroid cancer cell lines are either redundant or misidentified with cell lines of other tissue lineages has further hampered progress in the field. Of the available cell lines, 23 were identified as unique and presumably of thyroid origin based on the expression of thyroid-specific genes. Thus, there is a great need for validated thyroid cancer cell lines representing different stages of disease in addition to distinct oncogenic mutations. New, authenticated thyroid cancer cell lines are beginning to be developed, adding to the tools available to study genes and pathways important for thyroid cancer pathogenesis. In summary, the use of validated thyroid cancer cell lines that closely recapitulate disease is critical for the discovery of new drug targets and ultimately new therapies.
    Frontiers in Endocrinology 06/2012; 3:81. DOI:10.3389/fendo.2012.00081
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