This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blyth, K. Articles by Cameron, E. R. Search for Related Content PubMed PubMed Citation Articles by Blyth, K. Articles by Cameron, E. R.

Runx2 and MYC Collaborate in Lymphoma Development by Suppressing Apoptotic and Growth Arrest Pathways In vivo

Molecular Oncology Laboratory, Institute of Comparative Medicine, Faculty of Veterinary, Medicine, University of Glasgow, Glasgow, United Kingdom

Requests for reprints: Karen Blyth or Ewan R. Cameron, Molecular Oncology Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden, Glasgow G61 1QH, United Kingdom. Phone: 44-141-330-5726; Fax: 44-141-330-2271; E-mail: K.Blyth{at}vet.gla.ac.uk.

Members of the Runx and MYC families have been implicated as collaborating oncogenes. The mechanism of this potent collaboration is elucidated in this study of Runx2/MYC mice. As shown previously, ectopic expression of Runx2 in the thymus leads to a preneoplastic state defined by an accumulation of cells with an immature phenotype and a low proliferative rate. We now show that c-MYC overexpression is sufficient to rescue proliferation and to release the differentiation block imposed by Runx2. Analysis of Runx2-expressing lymphomas reveals a consistently low rate of apoptosis, in contrast to lymphomas of MYC mice which are often highly apoptotic. The low apoptosis phenotype is dominant in Runx2/MYC tumors, indicating that Runx2 confers a potent survival advantage to MYC-expressing tumor cells. The role of the p53 pathway in Runx2/MYC tumors was explored on a p53 heterozygote background. Surprisingly, functional p53 was retained in vivo, even after transplantation, whereas explanted tumor cells displayed rapid allele loss in vitro. Our results show that Runx2 and MYC overcome distinct "fail-safe" responses and that their selection as collaborating genes is due to their ability to neutralize each other's negative growth effect. Furthermore, the Runx2/MYC combination overcomes the requirement for genetic inactivation of the p53 pathway in vivo. (Cancer Res 2006; 66(4): 2195-201)

This article has been cited by other articles:

				M. Ravoet, C. Sibille, C. Gu, M. Libin, B. Haibe-Kains, C. Sotiriou, M. Goldman, F. Roufosse, and K. Willard-Gallo Molecular profiling of CD3-CD4+ T cells from patients with the lymphocytic variant of hypereosinophilic syndrome reveals targeting of growth control pathways Blood, October 1, 2009; 114(14): 2969 - 2983. [Abstract] [Full Text] [PDF]

				J. Pratap, K. M. Imbalzano, J. M. Underwood, N. Cohet, K. Gokul, J. Akech, A. J. van Wijnen, J. L. Stein, A. N. Imbalzano, J. A. Nickerson, et al. Ectopic Runx2 Expression in Mammary Epithelial Cells Disrupts Formation of Normal Acini Structure: Implications for Breast Cancer Progression Cancer Res., September 1, 2009; 69(17): 6807 - 6814. [Abstract] [Full Text] [PDF]

				C.-W. Chua, Y.-T. Chiu, H.-F. Yuen, K.-W. Chan, K. Man, X. Wang, M.-T. Ling, and Y.-C. Wong Suppression of Androgen-Independent Prostate Cancer Cell Aggressiveness by FTY720: Validating Runx2 as a Potential Antimetastatic Drug Screening Platform Clin. Cancer Res., July 1, 2009; 15(13): 4322 - 4335. [Abstract] [Full Text] [PDF]

				N. M. Teplyuk, Y. Zhang, Y. Lou, J. R. Hawse, M. Q. Hassan, V. I. Teplyuk, J. Pratap, M. Galindo, J. L. Stein, G. S. Stein, et al. The Osteogenic Transcription Factor Runx2 Controls Genes Involved in Sterol/Steroid Metabolism, Including Cyp11a1 in Osteoblasts Mol. Endocrinol., June 1, 2009; 23(6): 849 - 861. [Abstract] [Full Text] [PDF]

				N. M. Teplyuk, M. Galindo, V. I. Teplyuk, J. Pratap, D. W. Young, D. Lapointe, A. Javed, J. L. Stein, J. B. Lian, G. S. Stein, et al. Runx2 Regulates G Protein-coupled Signaling Pathways to Control Growth of Osteoblast Progenitors J. Biol. Chem., October 10, 2008; 283(41): 27585 - 27597. [Abstract] [Full Text] [PDF]

				J. Pratap, J. J. Wixted, T. Gaur, S. K. Zaidi, J. Dobson, K. D. Gokul, S. Hussain, A. J. van Wijnen, J. L. Stein, G. S. Stein, et al. Runx2 Transcriptional Activation of Indian Hedgehog and a Downstream Bone Metastatic Pathway in Breast Cancer Cells Cancer Res., October 1, 2008; 68(19): 7795 - 7802. [Abstract] [Full Text] [PDF]

				S. K. Zaidi, S. Pande, J. Pratap, T. Gaur, S. Grigoriu, S. A. Ali, J. L. Stein, J. B. Lian, A. J. van Wijnen, and G. S. Stein Runx2 deficiency and defective subnuclear targeting bypass senescence to promote immortalization and tumorigenic potential PNAS, December 11, 2007; 104(50): 19861 - 19866. [Abstract] [Full Text] [PDF]

				A. Kilbey, K. Blyth, S. Wotton, A. Terry, A. Jenkins, M. Bell, L. Hanlon, E. R. Cameron, and J. C. Neil Runx2 Disruption Promotes Immortalization and Confers Resistance to Oncogene-Induced Senescence in Primary Murine Fibroblasts Cancer Res., December 1, 2007; 67(23): 11263 - 11271. [Abstract] [Full Text] [PDF]

				G. Paroni, A. Fontanini, N. Cernotta, C. Foti, M. P. Gupta, X.-J. Yang, D. Fasino, and C. Brancolini Dephosphorylation and Caspase Processing Generate Distinct Nuclear Pools of Histone Deacetylase 4 Mol. Cell. Biol., October 1, 2007; 27(19): 6718 - 6732. [Abstract] [Full Text] [PDF]

				M. Stewart, N. Mackay, L. Hanlon, K. Blyth, L. Scobie, E. Cameron, and J. C. Neil Insertional Mutagenesis Reveals Progression Genes and Checkpoints in MYC/Runx2 Lymphomas Cancer Res., June 1, 2007; 67(11): 5126 - 5133. [Abstract] [Full Text] [PDF]