Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have ectopically expressed transcription factor ETS1 in two different highly tumorigenic human colon cancer cell lines, DLD-1 and HCT116, that do not express endogenous ETS1 protein and have obtained several independent clones. The expression of wild-type ETS1 protein in these colon cancer cells reverses the transformed phenotype and tumorigenicity in a dose-dependent manner. By contrast, expression in DLD-1 cells of a variant form of ETS1, lacking transcriptional activity, did not alter the tumorigenic properties of the cells, suggesting that the reduction in tumorigenicity in these clones was specific for the wild-type ETS1 gene products. Since these colon cancer cells have multiple genetic alterations, the system described in this paper could be a good model to study the suppression of tumorigenicity at a transcriptional level, which could lead to the design and development of novel drugs for cancer treatment.
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PMID:ETS1 suppresses tumorigenicity of human colon cancer cells. 775 25

We have previously shown that the human ETS1 protein (p51-ETS1), when ectopically expressed in colon cancer cell lines, is able to reduce its tumorigenicity without affecting its growth properties. To understand the mechanism of tumor reduction, we have expressed two different forms of ETS1 in colon cancer cell lines. Data presented in this paper indicate that the naturally occurring spliced variant protein, p42-ETS1, lacking the region encoded by ETS1 exon VII, represses the tumorigenicity, while p51-ETS1 reduces the tumorigenicity. Repression of tumorigenicity mediated by p42-ETS1 appears to be caused by its ability to induce apoptosis in epithelial cancer cells. This work can have profound medical significance in that it may open up new insights into the potential role of the p42-ETS1 in the induction of apoptosis in epithelial cell cancers and may provide a rationale for its use for potential gene therapy experiments to initiate cell death in cancer cells.
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PMID:A variant form of ETS1 induces apoptosis in human colon cancer cells. 926 72

ETS1, the founding member of Ets transcriptional factor family, plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Previous work has shown that ETS1 represses tumorigenicity of colon carcinoma cells in vivo, and that the p42-ETS1 protein bypasses a defect in apoptosis in colon carcinoma cells through the up-regulation of caspase-1 expression. In this report, we show that expression of p42-ETS1 inhibits tumorigenicity of colon cancer DLD-1 cells through induction of apoptosis in vivo. In support of the hypothesis that caspase-1 might be a target involved in the sensitization of DLD-1 cells to Fas-induced apoptosis by ETS1, overexpression of caspase-1 bypasses Fas-induced apoptosis in these cells as well. Furthermore, ETS1-mediated apoptosis was observed in MOP8 cells, a transformed mouse NIH3T3 cell line. To determine whether ETS1 activates the transcription of caspase-1, luciferase reporters driven by the wild-type and mutant caspase-1 promoters were generated. Both p51-ETS1 and p42-ETS1 transactivated the caspase-1 transcription and a functional Ets binding site is identified in the caspase-1 promoter. Wild-type caspase-1 promoter (pGL3-ICE) was strongly transactivated by ETS1 and this transactivation was dramatically diminished by the mutation of the potential Ets binding site (-525 bp). In addition, electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed complex formation between this binding site and ETS1 proteins. Taken together, ETS1 transcriptionally induces the expression of caspase-1; as such, the regulatory control of caspase-1 expression by ETS1 may underlie the apoptotic susceptibility modulated by ETS1 in specific tumor cells.
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PMID:Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced apoptosis. 1610 71

We have previously shown that the ETS1 gene is expressed in a tissue-specific manner, and encodes a transcription factor, that may be involved in lymphocyte development, activation and proliferation. To understand the ETS1 function in non-lymphoid cells, we have ectopically expressed ETS1 protein in a human colon cancer cell line, and studied its biochemical properties. The 51 kDa ETS1 protein expressed in transfected cells localized in both the nucleus and the cytoplasm, has similar biochemical properties compared to ETS1 protein expressed in lymphoid cells. The ectopically expressed ETS1 binds to the DNA in sequence-specific manner and the binding activity is affected by the flanking sequences outside the 'GGA' core. Our results also demonstrate that the DNA-binding activity of full-length ETS1 is similar in lymphoid and non-lymphoid cells. The ETS1 expressed in DLD-1 cells is biologically active since it induces a 54.5 kDa polypeptide, whose expression level correlates with the expression of ETS1 in DLD-1 cells.
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PMID:Characterization of ectopically-expressed ets1 in human colon-cancer cells - induction of putative ets1-target gene. 2157 1

New evidence suggests that microRNAs (miRNAs) play an important role in regulating the development and progression of prostate cancer. However, their specific functions and mechanisms remained to be further explored. MiR-129 has been reported in gastric cancers, colon cancer and lung cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in prostate cancer. The purpose of our study is to clarify the effects of miR-129 in cellular processes correlated with cancer development and progression of prostate cancer cell by regulating ETS1. MiR-129 and ETS1 expression in prostate cancer tissues, tumor adjacent tissues and cells were tested by quantitative real-time PCR. We validated the target relationship between miR-129 and ETS1 by dual luciferase reporter gene system. MTT, colony formation, tumorigenesis assays, flow cytometry, wound healing and transwell assays were used to analyze cell viability, proliferation, migration, and invasiveness in vivo and in vitro. The level of ETS1 protein expression was detected by western blot. Here we demonstrate that miR-129 have a relatively reduced expression in prostate cancer cell lines and tissues. Morever, the miR-129 inhibits the expression of ETS1 by binding its 3'-UTR. The overexpression of miR-129 can inhibit PC-3 cell viability, proliferation, migration and invasion through targeting ETS1 by PI3K/AKT/mTOR signaling pathway. These findings suggested that miR-129 could directly suppress ETS1, which might be one of potential mechanisms in inhibiting cell processes including viability, proliferation, migration and invasiveness of prostate cancercells and it provides new clues for us to understand the carcinogenesis of prostate cancer. In addition, it may help to develop a treatment approach for ETS1-activated prostate cancer.
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PMID:MiR-129 inhibits cell proliferation and metastasis by targeting ETS1 via PI3K/AKT/mTOR pathway in prostate cancer. 2903 29