Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ets genes encode eukaryotic transcription factors that are involved in tumorigenesis and developmental processes. The signature of the Ets family is the ETS-domain, which binds to sites containing a central 5'-GGAA/T-3' motif. They can be sub-classified primarily because of the high amino acid conservation in their ETS-domains and, in addition, in the conservation of other domains generally characterized as transactivating. This is the case for the PEA3 group, which is currently made up of three members, PEA3/E1AF, ER81/ETV1 and ERM, which are more than 95% identical in the ETS-domain and more than 85% in the transactivation acidic domain. The members of the PEA3 group are activated through both the Ras-dependent and other kinase pathways, a function which emphasizes their involvement in several oncogenic mechanisms. The expression pattern of the three PEA3 group genes during mouse embryogenesis suggests that they are differentially regulated, probably to serve important functions such as tissue interaction. Although the target genes of these transcription factors are multiple, their most frequently studied role concerns their involvement in the metastatic process. In fact, PEA3 group members are over-expressed in metastatic human breast cancer cells and mouse mammary tumors, a feature which suggests a function of these transcription factors in mammary oncogenesis. Moreover, when they are ectopically over-expressed in non-metastatic breast cancer cells, these latter become metastatic with the activation of transcription of matrix metalloproteinases or adhesion molecules, such as ICAM-1.
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PMID:The PEA3 group of ETS-related transcription factors. Role in breast cancer metastasis. 1095 16

The remodeling of extracellular matrix (ECM) is an important process required for cancer cells to turn into invasive and metastatic cancer cells. To dissolve the protein components of ECM, matrix metalloproteinases are some of the essential enzymes. Another ECM remodeling enzyme is the heparanase (Hpa) that digests the heparin sulfate component of the matrix. In metastatic cancer cells the Hpa gene is upregulated. To investigate the mechanism of why Hpa was upregulated in metastatic cancer cells, the regulatory sequence of heparanase gene was isolated and its function analysed in metastatic breast cancer cells. We found there are four ETS transcription factor binding sites. Two of them flanking the transcription initiation of the Hpa gene are nonfunctional, whereas two others are highly functional and responded to exogenously added ETS transcription factors. Mutation of these two ETS binding sites abolished the transcriptional activation of Hpa promoter by ETS transcription factors. Among four transcription factors tested (ETS1, ETS2, PEA3, and ER81), ETS1 and ETS2 are more potent in transactivating the human Hpa gene. Furthermore, dominant-negative ETS transcription factors failed to transactivate Hpa promoter and could abrogate the function of wild-type transcription factor in transactivation activity of ETS transcription factors on the Hpa promoter. These results suggest that ETS transcription factors play an important role in tumor invasion and metastasis by modulating the remodeling of ECM.
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PMID:Trans-activation of heparanase promoter by ETS transcription factors. 1258 71