HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tikhonenko, A. T. Articles by Linial, M. L. Search for Related Content PubMed PubMed Citation Articles by Tikhonenko, A. T. Articles by Linial, M. L. Social Bookmarking                      What's this?

Volume 271, Number 48, Issue of November 29, 1996 pp. 30741-30747
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Viral Myc Oncoproteins in Infected Fibroblasts Down-modulate Thrombospondin-1, a Possible Tumor Suppressor Gene

(Received for publication, June 28, 1996, and in revised form, September 5, 1996)

From the Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104

We are interested in identifying the transcriptional targets of the Myc oncoproteins. To this end, we have fused Myc of the MC29 retrovirus with the rat glucocorticoid receptor. This chimeric protein requires dexamethasone to undergo nuclear translocation and achieve an active conformation. We employed a differential hybridization approach to identify mRNAs that are induced or repressed in infected avian fibroblasts in response to dexamethasone. This screen yielded one mRNA underrepresented in the dexamethasone-treated cells. In Myc-transformed cell clones, its level decreases 6-fold as early as 4 h and more than 30-fold after 32 h of exposure to the hormone. This mRNA was also down-regulated by recombinant Myc retroviruses in rodent fibroblasts, including those refractory to transformation.

Sequence analysis revealed that it is homologous to the 3 untranslated regions of the mammalian thrombospondin-1 genes. Using an anti-thrombospondin antibody, we confirmed that rodent cells overexpressing Myc produce very small amounts of this protein. Also, they do not support efficient expression of a reporter gene driven by the thrombospondin-1 promoter. Thus, thrombospondin-1 is a bona fide target of Myc. Moreover, its silencing might pertain to the transforming activity of Myc, since in several systems thrombospondin-1 exhibits tumor suppressor properties, presumably due to its negative effect on neovascularization.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Yekkala and T. A. Baudino Inhibition of Intestinal Polyposis with Reduced Angiogenesis in ApcMin/+ Mice Due to Decreases in c-Myc Expression Mol. Cancer Res., December 1, 2007; 5(12): 1296 - 1303. [Abstract] [Full Text] [PDF]

				G. Potikyan, R. O.V. Savene, J. M. Gaulden, K. A. France, Z. Zhou, E. S. Kleinerman, S. L. Lessnick, and C. T. Denny EWS/FLI1 Regulates Tumor Angiogenesis in Ewing's Sarcoma via Suppression of Thrombospondins Cancer Res., July 15, 2007; 67(14): 6675 - 6684. [Abstract] [Full Text] [PDF]

				Z. Li, C. Wang, X. Jiao, Y. Lu, M. Fu, A. A. Quong, C. Dye, J. Yang, M. Dai, X. Ju, et al. Cyclin D1 Regulates Cellular Migration through the Inhibition of Thrombospondin 1 and ROCK Signaling. Mol. Cell. Biol., June 1, 2006; 26(11): 4240 - 4256. [Abstract] [Full Text] [PDF]

				U. E. Knies-Bamforth, S. B. Fox, R. Poulsom, G. I. Evan, and A. L. Harris c-Myc Interacts with Hypoxia to Induce Angiogenesis In vivo by a Vascular Endothelial Growth Factor-Dependent Mechanism Cancer Res., September 15, 2004; 64(18): 6563 - 6570. [Abstract] [Full Text] [PDF]

				A. Thomas-Tikhonenko, I. Viard-Leveugle, M. Dews, P. Wehrli, C. Sevignani, D. Yu, S. Ricci, W. el-Deiry, B. Aronow, G. Kaya, et al. Myc-Transformed Epithelial Cells Down-Regulate Clusterin, Which Inhibits Their Growth in Vitro and Carcinogenesis in Vivo Cancer Res., May 1, 2004; 64(9): 3126 - 3136. [Abstract] [Full Text] [PDF]

				Y.-W. Zhang, Y. Su, O. V. Volpert, and G. F. V. Woude Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation PNAS, October 28, 2003; 100(22): 12718 - 12723. [Abstract] [Full Text] [PDF]

				T. A. Baudino, C. McKay, H. Pendeville-Samain, J. A. Nilsson, K. H. Maclean, E. L. White, A. C. Davis, J. N. Ihle, and J. L. Cleveland c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression Genes & Dev., October 1, 2002; 16(19): 2530 - 2543. [Abstract] [Full Text] [PDF]

				S. Filleur, O. V. Volpert, A. Degeorges, C. Voland, F. Reiher, P. Clezardin, N. Bouck, and F. Cabon In vivo mechanisms by which tumors producing thrombospondin 1 bypass its inhibitory effects Genes & Dev., June 1, 2001; 15(11): 1373 - 1382. [Abstract] [Full Text] [PDF]

				K. R. Laderoute, R. M. Alarcon, M. D. Brody, J. M. Calaoagan, E. Y. Chen, A. M. Knapp, Z. Yun, N. C. Denko, and A. J. Giaccia Opposing Effects of Hypoxia on Expression of the Angiogenic Inhibitor Thrombospondin 1 and the Angiogenic Inducer Vascular Endothelial Growth Factor Clin. Cancer Res., July 1, 2000; 6(7): 2941 - 2950. [Abstract] [Full Text]

				A. Janz, C. Sevignani, K. Kenyon, C. V. Ngo, and A. Thomas-Tikhonenko Activation of the Myc oncoprotein leads to increased turnover of thrombospondin-1 mRNA Nucleic Acids Res., June 1, 2000; 28(11): 2268 - 2275. [Abstract] [Full Text] [PDF]

				C. V. Ngo, M. Gee, N. Akhtar, D. Yu, O. Volpert, R. Auerbach, and A. Thomas-Tikhonenko An in Vivo Function for the Transforming Myc Protein: Elicitation of the Angiogenic Phenotype Cell Growth Differ., April 1, 2000; 11(4): 201 - 210. [Abstract] [Full Text]

				J. D. Banks and M. L. Linial Secondary Structure Analysis of a Minimal Avian Leukosis-Sarcoma Virus Packaging Signal J. Virol., January 1, 2000; 74(1): 456 - 464. [Abstract] [Full Text]

				J. D. Banks, B. O. Kealoha, and M. L. Linial An MPsi -Containing Heterologous RNA, but Not env mRNA, Is Efficiently Packaged into Avian Retroviral Particles J. Virol., November 1, 1999; 73(11): 8926 - 8933. [Abstract] [Full Text] [PDF]

				K. O. Mitchell and W. S. El-Deiry Overexpression of c-Myc Inhibits p21WAF1/CIP1 Expression and Induces S-Phase Entry in 12-O-Tetradecanoylphorbol-13-acetate (TPA)-sensitive Human Cancer Cells Cell Growth Differ., April 1, 1999; 10(4): 223 - 230. [Abstract] [Full Text]

				X. Wang, M. A. Peters, F. E. Utama, Y. Wang, and E. J. Taparowsky The Adrenomedullin Gene Is a Target for Negative Regulation by the Myc Transcription Complex Mol. Endocrinol., February 1, 1999; 13(2): 254 - 267. [Abstract] [Full Text]

				C. V. Dang c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism Mol. Cell. Biol., January 1, 1999; 19(1): 1 - 11. [Full Text] [PDF]

				K. Bein, J. A. Ware, and M. Simons Myb-dependent Regulation of Thrombospondin 2 Expression. ROLE OF mRNA STABILITY J. Biol. Chem., August 14, 1998; 273(33): 21423 - 21429. [Abstract] [Full Text] [PDF]

				L. Facchini and L. Z. Penn The molecular role of Myc in growth and transformation: recent discoveries lead to new insights FASEB J, June 1, 1998; 12(9): 633 - 651. [Abstract] [Full Text]