EWS/ETS Fusions Activate Telomerase in Ewing's Tumors

Cancer Research

Volumn 63, Issue 23, 2003, Pages 8338-8344

  Takahashi, Akiko ^a   Higashino, Fumihiro ^a   Aoyagi, Mariko ^a   Yoshida, Koichi ^b   Itoh, Miyuki ^b   Kyo, Satoru ^c   Ohno, Takatoshi ^d   Taira, Takahiro ^a   Ariga, Hiroyoshi ^a   Nakajima, Kohichi ^e   Hatta, Mitsutoki ^a   Kobayashi, Masanobu ^a   Sano, Hidehiko ^a   Kohgo, Takao ^a   Shindoh, Masanobu ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

^b SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c KANAZAWA UNIV SCHOOL OF MEDICINE   (Japan)

^d GIFU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^e OSAKA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CHIMERIC PROTEIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; EWS E1AF PROTEIN; EWS ETS PROTEIN; EWS FLI1 PROTEIN; HYBRID PROTEIN; PROTEIN; RNA DIRECTED DNA POLYMERASE; TELOMERASE REVERSE TRANSCRIPTASE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ARTICLE; CANCER CELL CULTURE; CELL TRANSFORMATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; EWING SARCOMA; GENE; GENE EXPRESSION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

ADENOVIRUS E1A PROTEINS; ANIMALS; CELL LINE, TUMOR; DNA-BINDING PROTEINS; ENZYME ACTIVATION; HELA CELLS; HUMANS; MICE; NIH 3T3 CELLS; ONCOGENE PROTEINS, FUSION; PROMOTER REGIONS (GENETICS); PROTO-ONCOGENE PROTEIN C-FLI-1; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-ETS; RNA INTERFERENCE; RNA, MESSENGER; SARCOMA, EWING'S; TELOMERASE; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION FACTORS;

EID: 10744231438     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (50)

1. Arvand, A., and Denny, C. T. Biology of EWS/ETS fusions in Ewing's family tumors. Oncogene, 20: 5747-5754, 2001.
2. 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 (Lond.), 359: 162-165, 1992.
3. Ben-David, Y., Giddens, E. B., and Bernstein, A. Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus. Proc. Natl. Acad. Sci. USA, 87: 1332-1336, 1990.
4. Rao, V. N., Ohno, T., Prasad, D. D., Bhattacharya, G., and Reddy, E. S. Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein. Oncogene, 8: 2167-2173, 1993.
5. May, W. A., Lessnick, S. L., Braun, B. S., Klemsz, M., Lewis, B. C., Lunsford, L. B., Hromas, R., and Denny, C. T. The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol. Cell. Biol., 13: 7393-7398, 1993.
6. Ohno, T., Rao, V. N., and Reddy, E. S. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res., 53: 5859-5863, 1993.
7. Bailly, R. A., Bosselut, R., Zucman, J., Cormier, F., Delattre, O., Roussel, M., Thomas, G., and Ghysdael, J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol. Cell. Biol., 14: 3230-3241. 1994.
8. Mao, X., Miesfeldt, S., Yang, H., Leiden, J. M., and Thompson, C. B. The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities. J. Biol. Chem., 269: 18216-18222, 1994.
9. Magnaghi-Jaulin, L., Masutani, H., Robin. P., Lipinski, M., and Harel-Bellan, A. SRE elements are binding sites for the fusion protein EWS-FLI-1. Nucleic Acids Res., 24: 1052-1058, 1996.
10. Zwerner, J. P., and May, W. A. PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors. Oncogene, 20: 626-633, 2001.
11. Zwemer. J. P., and May. W. A. Dominant negative PDGF-C inhibits growth of Ewing family tumor cell lines. Oncogene, 21: 3847-3854, 2002.
12. Nishimori, H., Sasaki, Y., Yoshida, K., Irifune, H., Zembutsu, H., Tanaka, T., Aoyama, T., Hosaka, T., Kawaguchi, S., Wada, T., Hata, J., Toguchida, J., Nakamura, Y., and Tokino, T. The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors. Oncogene. 21: 8302-8309, 2002.
13. Higashino, F., Yoshida, K., Fujinaga, Y., 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. Nucleic Acids Res., 21: 547-553, 1993.
14. 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.
15. Kaya, M., Yoshida, K., Higashino, F., Mitaka, T., Ishii, S., and Fujinaga, K. A single ets-related transcription factor, E1AF, confers invasive phenotype on human cancer cells. Oncogene, 12: 221-227, 1996.
16. Shindoh, M., Higashino, F., Kaya, M., Yasuda, M., Funaoka, K., Hanzawa, M., Hida, K., Kohgo, T., Amemiya, A., Yoshida, K., and Fujinaga. K. Correlated expression of matrix metalloproteinases and ets family transcription factor E1A-F in invasive oral squamous-cell-carcinoma-derived cell lines. Am. J. Pathol., 148: 693-700, 1996.
17. Blasco, M. A., Lee, H. W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., and Greider, C. W. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell, 91: 25-34, 1997.
18. Shay, J. W. Telomerase in human development and cancer. J. Cell. Physiol., 173: 266-270, 1997.
19. Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., and Wright, W. E. Extension of life-span by introduction of telomerase into normal human cells. Science (Wash. DC), 279: 349-352, 1998.
20. Takakura, M., Kyo, S., Kanaya. T., Hirano, H., Takeda, J., Yutsudo, M., and Inoue, M. Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res., 59: 551-557, 1999.
21. Greenberg, R. A., O'Hagan, R. C., Deng, H., Xiao, Q., Hann, S. R., Adams, R. R., Lichtsteiner, S., Chin, L., Morin, G. B., and DePinho, R. A. Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene, 18: 1219-1226. 1999.
22. Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., Fujimoto, K., Nishio, Y., Orimo, A., Inoue. M. Estrogen activates telomerase Cancer Res., 59: 5917-5921, 1999.
23. Kanaya, T., Kyo, S., Hamada, K., Takakura, M., Kitagawa, Y., Harada, H., and Inoue, M. Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription. Clin. Cancer Res., 6: 1239-1247, 2000.
24. Yang, H., Kyo, S., Takatura. M., and Sun, L. Autocrine transforming growth factor suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells. Cell Growth Differ., 12: 119-127, 2001.
25. Maida, Y., Kyo, S., Kanaya, T., Wang, Z., Yatabe, N., Tanaka, M., Nakamura, M., Ohmichi, M., Gotoh, N., Murakami, S., and Inoue, M. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene, 21: 4071-4079, 2002.
26. Wang, J., Xie, L. Y., Allan, S., Beach, D., and Hannon, G. J. Myc activates telomerase. Genes Dev., 12: 1769-1774, 1998.
27. Wu, K. J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R. Direct activation of TERT transcription by c-MYC. Nat. Genet., 21: 220-224, 1999.
28. Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H., and Inoue, M. Spl cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res., 28: 669-677, 2000.
29. Taira, T., Maeda, J., Onishi, T., Kitaura, H., Yoshida, S., Kato, H., Ikeda, M., Tamai, K., Iguchi-Ariga, S. M., and Ariga, H. AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC. Genes Cells, 3: 549-565, 1998.
30. Ouchida, M., Ohno, T., Fujimura, Y., Rao, V. N., and Reddy, E. S. Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene, 11: 1049-1054, 1995.
31. 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-EIAF, available for diagnosis. Jpn. J. Cancer Res., 89: 703-711, 1998.
32. Martin-Rivera, L., Herrera, E., Albar, J. P., and Blasco, M. A. Expression of mouse telomerase catalytic subunit in embryos and adult tissues. Proc. Natl. Acad. Sci. USA, 95: 10471-10476, 1998.
33. Benkoussa, M., Brand, C., Delmotte, M. H., Formstecher, P., and Lefebvre, P. Retinoic acid receptors inhibit API activation by regulating extracellular signal-regulated kinase and CBP recruitment to an APl-responsive promoter. Mol. Cell. Biol., 22: 4522-4534, 2002.
34. Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S. L., and Shay, J. W. Specific association of human telomerase activity with immortal cells and cancer. Science (Wash. DC), 266: 2011-2015, 1994.
35. Nakae, K., Nakajima, K., Inazawa, J., Kitaoka, T., and Hirano, T. ERM, a PEA3 subfamily of Ets transcription factors, can cooperate with c-Jun. J. Biol. Chem., 270: 23795-23800, 1995.
36. Rossow, K. L., and Janknecht, R. The Ewing's sarcoma gene product functions as a transcriptional activator. Cancer Res., 61: 2690-2695, 2001.
37. Araya, N., Hirota, K., Shimamoto, Y., Miyagishi, M., Yoshida, E., Ishida, J., Kaneko, S., Kaneko, M., Nakajima, T., and Fukamizu, A. Cooperative interaction of EWS with CBP selectively activates HNF4-mediated transcription. J. Biol. Chem., 278: 5427-5432, 2003.
38. Fujimura, Y., Siddique, H., Lee, L., Rao, V. N., and Reddy, E. S. EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function. Oncogene, 20: 6653-6659, 2001.
39. Giles, R. H., Peters, D. J., and Breuning, M. H. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet., 14: 178-183, 1998.
40. Hahm, K. B., Cho, K., Lee, C., Im, Y. H., Chang, J., Choi, S. G., Sorensen, P. H., Thiele, C. J., and Kim, S. J. Repression of the gene encoding the TGF-β type 11 receptor is a major target of the EWS-FLI1 oncoprotein. Nat. Genet., 23: 222-227, 1999.
41. Im, Y. H., Kim, H. T., Lee, C., Poulin, D., Welford, S., Sorensen, P. H., Denny, C. T., and Kim, S. J. EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor β type 11 receptor gene. Cancer Res., 60: 1536-1540, 2000.
42. Kyo, S., and Inoue, M. Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy? Oncogene, 21: 688-697, 2002.
43. Jaishankar, S., Zhang, J., Roussel, M. F., and Baker, S. J. Transforming activity of EWS/FLI is not strictly dependent upon DNA-binding activity. Oncogene, 18: 5592-5597, 1999.
44. Welford, S. M., Hebert, S. P., Deneen, B., Arvand, A., and Denny, C. T. DNA binding domain-independent pathways are involved in EWS/FL11-mediated oncogenesis. J. Biol. Chem., 276: 41977-41984, 2001.
45. Dauphinot, L., De, Oliveira, C., Melot, T., Sevenet, N., Thomas, V., Weissman, B. E., and Delattre, O. Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2and c-Myc expression. Oncogene, 20: 3258-3265, 2001.
46. Bertolotti, A., Melot, T., Acker, J., Vigneron, M., Delattre, O., and Tora, L. EWS, but not EWS-FLI-1, is associated with both TF11D and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes. Mol. Cell. Biol., 18: 1489-1497, 1998.
47. Bertolotti, A., Bell, B., and Tora, L. The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties. Oncogene, 18: 8000-8010, 1999.
48. Tomoda, R., Seto, M., Tsumuki, H., Iida, K., Yamazaki, T., Sonoda, J., Matsumine, A., and Uchida, A. Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors. Cancer (Phila.), 95: 1127-1133, 2002.
49. Zhao, H. H., Herrera, R. E., Coronado-Heinsohn, E., Yang, M. C., Ludes-Meyers, J. H., Seybold-Tilson, K. J., Nawaz, Z., Yee, D., Barr, F. G., Diab, S. G., Brown, P. H., Fuqua, S. A., and Osborne, C. K. Forkhead homologue in rhabdomyosarcoma functions as a bifunctional nuclear receptor-interacting protein with both coactivator and corepressor functions. J. Biol. Chem., 276: 27907-27912, 2001.
50. Hirota, K., Daitoku, H., Matsuzaki, H., Araya, N., Yamagata, K., Asada, S., Sugaya, T., and Fukamizu, A. Hepatocyte nuclear factor-4 is a novel downstream target of insulin via FKHR as a signal-regulated transcriptional inhibitor. J. Biol. Chem., 278: 13056-13060, 2003.