Abstract
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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References
Sharrocks A. D., Brown A. L., Ling Y. and Yates P. R., The ETS domain transcription factor family. Int. J. Biochem. Cell. Biol. 29, 12, 1371–1387, 1997
Dittmer J. and Nordheim A., Ets transcription factors and human disease. Biochem. Biophys. Acta. 1377, F1–F11, 1998
Karim F. D., Umess L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. A. and Graves B. J., The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 4, 9, 1451–1453, 1990
Xin J. H., Cowie A., Lachance P. and Hassell J. A., Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. Genes Dev. 6, 481–496, 1992
Higashino F., Yoshida K., Kamio K. and Fujinaga K., Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene family. Nucl. Acid Res. 21, 547–553, 1993
Friedman L. S., Ostermeyer E. A., Lynch E. D., Szabo C. I., Anderson L. A., Dowd P., Lee M. K., Rowell S. E., Boyd J. and King M. C., The search for BRCA1. Cancer Res. 54, 24, 6374–82, 1994
Brown T. A. and McKnight S. L., Specificities of protein-protein and protein-DNA interaction of GABPa and two newly defined ets-related proteins. Genes Dev. 6, 2502–2512, 1992
Jeon I. S., Davis J. N., Braun B. S., Sublett J. E., Roussel M. F., Denny C. T. and Shapiro D. N., A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 10, 6, 1229–1234, 1995
Monte D., Coutte L., Baert J.-L., Angeli I., Stéhelin D. and de Launoit Y., Molecular characterization of the Ets-related human transcription factor ER81. Oncogene 11, 771–780, 1995
Monte D., Baert J.-L., Defossez P.-A., de Launoit Y. and Stéhelin D., Molecular cloning and characterization of human ERM, a new member of the ETS family closely related to mouse PEA3 and ER81 transcription factors. Oncogene 9, 1397–1406, 1994
Nakae K., Nakajima K., Inazawa J., Kitaoka T. and Hirano T., ERM, a member of the PEA3 subfamily of Ets transcription factors, can cooperate with c-jun. J. Biol. Chem. 270, 40, 23795–23800, 1995
Chotteau-Lelièvre A., Desbiens X., Pelczar H., Defossez P.-A. and De Launoit Y., Differential expression patterns of the PEA3 group transcription factors through murine embryonic development. Oncogene 15, 937–952, 1997
de Launoit Y., Baert J.-L., Chotteau A., Monté D., Defossez P.-A., Coutte L., Pelczar H. and Leenders F., Structure-function relationships of the PEA3 group of Ets-related transcription factors. Biochem. Mol. Med. 61, 2, 127–35, 1997
Monté D., Coutte L., Dewitte F., Defossez P.-A., Le Coniat M., Stéhelin D., Berger R. and de Launoit Y., Genomic organization of the human ERM (ETV5) gene, a PEA3 group member of ETS transcription factors. Genomics 35, 1, 236–240, 1996
Coutte L., Monte D., Imai K., Pouilly L., Dewitte F., Vidaud M., Adamski J., Baert J.-L. and de Launoit Y., Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human. Oncogene in press, 1999
Coutte L., Monté D., Baert J.-L. and de Launoit Y., Genomic organization of the human E1A-F gene, a member of ETS transcription factors. Gene in press, 1999
Isobe M., Yamagichi F., Yoshida K., Higashino F. and Fujinaga K., Assignment of the ets-related transcription factor El AF gene (ETV4) to human chromosome region 17q21. Genomics 28, 357–359, 1995
Osborne-Lawrence S., Welcsh P. L., Spillman M., Chandrasekharappa S. C., Gallardo T. D., Lovett M. and Bowcock A. M., Direct selection of expressed sequences within a 1-Mb region flanking BRCA1 on human chromosome 17q21. Genomics 25, 1, 248–55, 1995
Brown L. A., Amores A., Schilling T. F., Jowett T., Baert J.-L., Ingham P. W., de Launoit Y. and Sharrocks A. D., Molecular characterisation of the zebrafish PEA3 ETS-domain transcription factor. Oncogene 17, 1, 93–104, 1998
Laget M.-P., Defossez P.-A., Albagli O., Baert J.-L., Dewitte F., Stéhelin D. and de Launoit Y., Two functionally distinct domains cooperate for transactivation by the ETS family member ERM. Oncogene 12, 6, 1325–1336, 1996
Janhecht R., Monté D., Baert J.-L. and de Launoit Y., The ETS-related transcription factor ERM is a nuclear target of signaling cascades involving MAPK and PKA. Oncogene 13, 8, 1745–1754, 1996
Higashino F., Yoshida K., Noumi T., Seiki M. and Fujinaga K., Ets-related protein E1A-F can activate three different matrix metalloproteinase gene promoters. Oncogene 10, 1461–1463, 1995
Chen J. H., Vercamer C., Li Z., Paulin D., Vandenbunder B. and Stehelin D., PEA3 transactivates vimentin promoter in mammary epithelial and tumor cells. Oncogene 13, 1667–1675, 1996
de Launoit Y., Audette M., Pelczar H., Plaza S. and Baert J.-L., The transcription of the intercellular adhesion molecule-1 is regulated by Ets transcription factors. Oncogene 16, 2065–2073, 1998
Janknecht R., Analysis of the EM-stimulated transcription factor ER81. Mol. Cell. Biol. 16, 1551–1556, 1996
Defossez P.-A., Baert J.-L., Monnot M. and de Launoit Y., The ETS family member ERM contains an alpha-helical acidic activation domain that contacts TAFII60. Nucleic Acids Res. 25, 22, 4455–4463, 1997
Schneikert J., Peterziel H., Defossez P.-A., Klocker H., de Launoit Y. and Cato A. C. B., Androgen receptor Ets protein interaction is a novel mechanism for steroid hormone mediated down regulation of matrix metalloproteinase expression. J. Biol. Chem. 271, 39, 23907–23913, 1996
Treisman R., Regulation of transcription by MAP kinase cascades. Curr. Opin. Cell Biol. 8, 2, 205–15, 1996
O’Hagan R. C., Tozer R. G., Symons M., McCormick F. and Hassell J. A., The activity of the Ets transcription factor PEA3 is regulated by two distinct MAPK cascades. Oncogene 13, 1323–1333, 1996
Hagedorn L., Paratore C., Mercader N., Brognoli G., Baert J.-L., Suter U. and Sommer L., The Ets domain transcription factor Erm distinguishes satellite glia from Schwann cells and is maintained in satellite cells by neuregulin signalling. submitted 1999
Munchberg S. R. and Steinbeisser H., The Xenopus Ets transcription factor XER81 is a target of the FGF signaling pathway. Mech. Dev. 80, 1, 53–65, 1999
Lin J. H., Saito T., Anderson D. J., Lance-Jones C., Jessell T. M. and Arber S., Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell 95, 3, 393–407, 1998
Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., De Jong P., Rouleau G., Aurias A. and Thomas G., Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 6391, 162–165, 1992
Zucman J., Melot T., Desmaze C., Ghysdael J., Plougastel B., Peter M., Zucker J. M., Triche T. J., Sheer D., Turc-Carel C., Ambros P., Combaret V., Lenoir G., Aurias A., Thomas G. and Delattre O., Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J. 12, 4481–4487, 1993
Kaneko Y., Yoshida K., Handa M., Toyoda Y., Nishihira H., Tanaka Y., Sasaki Y., Ishida S., Higashino F. and Fujinaga K., Fusion of an ETS-family gene, EIAF, to EWS by t( 17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer 15, 2, 115–121, 1996
Ishida S., Yoshida K., Kaneko Y., Tanaka Y., Sasaki Y., Urano F., Umezawa A., Hata J. and Fujinaga K., The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma. Cytogenet. Cell Genet. 82, 3–4, 278–83, 1998
Urano F., Umezawa A., Yabe H., Hong W., Yoshida K., Fujinaga K. and Hata J., Molecular analysis of Ewing’s sarcoma: another fusion gene, EWS-E1 AF, available for diagnosis. Jpn. J. Cancer Res. 89, 7, 703–11, 1998
Braun B. S., Frieden R., Lessnick S. L., May W. A. and Denny C. T., Identification of target genes for the ewing’s sarcoma EWS/FLI fusion protein by representational difference analysis. Mol. Cell. Biol. 15, 8, 4623–4630, 1995
Baert J.-L., Monte D., Musgrove E. A., Albagli O., Sutherland R. L. and de Launoit Y., Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells. Int. J. Cancer 70, 590–597, 1997
Trimble M. S., Xin J. H., Guy C. T., Muller W. J. and Hassell J. A., PEA3 is overexpressed in mouse metastatic mammary adenocarcinomas. Oncogene 8, 3037–3042, 1993
Kaya M., Yoshida K., Higashino F., Mitaka T., Ishii S. and Fujinaga K., A single ets-related transcription factor, El AF, confers invasive phenotype on human cancer cells. Oncogene 12, 22 1–227, 1996
Habelhah H., Okada F., Kobayashi M., Nakai K., Choi S., Hamada J., Moriuchi T., Kaya M., Yoshida K., Fujinaga K. and Hosokawa M., Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression. Oncogene 18, 9, 1771–6, 1999
Hida K., Shindoh M., Yasuda M., Hanzawa M., Funaoka K., Kohgo T., Amemiya A., Totsuka Y., Yoshida K. and Fujinaga K., Antisense E1AF transfection restrains oral cancer invasion by reducing matrix metalloproteinase activities. Am. J. Pathol. 150, 6, 2125–2132, 1997
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de Launoit, Y. et al. (2002). The PEA3 Group of ETS-related Transcription Factors. In: Mol, J.A., Clegg, R.A. (eds) Biology of the Mammary Gland. Advances in Experimental Medicine and Biology, vol 480. Springer, Boston, MA. https://doi.org/10.1007/0-306-46832-8_13
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DOI: https://doi.org/10.1007/0-306-46832-8_13
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