This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Lerga, A. Articles by León, J. Search for Related Content PubMed PubMed Citation Articles by Lerga, A. Articles by León, J.

Regulation of c-Myc and Max in Megakaryocytic and Monocytic-Macrophagic Differentiation of K562 Cells Induced by Protein Kinase C Modifiers: c-Myc Is Down-Regulated but Does Not Inhibit Differentiation¹

Grupo de Biología Molecular del Cáncer, Departamento de Biología Molecular-Unidad Asociada al Centro de Investigaciones Biológicas del CSIC [A. L., P. C., M. D. D., M. C., E. C., P. G., N. A., J. L.] and Departamento de Anatomía y Biología Celular [M. B.], Universidad de Cantabria, and Servicio de Hematología, Hospital Universitario Marqués de Valdecilla [C. R.], Santander, Spain; Departamento de Bioquímica, Universidad Autónoma de Madrid, Spain [C. C.]; and National Institute of Dental Research, NIH, Bethesda, Maryland [S. G.]

We have studied the regulation and role of c-Myc and Max in the differentiation pathways induced in K562 cells by 12-O-tetradecanoyl phorbol-13 acetate (TPA) and staurosporine, an activator and inhibitor, respectively, of protein kinase C (PKC). We found that staurosporine induced megakaryocytic differentiation, as revealed by the cellular ultrastructure, platelet formation, and DNA endoreduplication. In contrast, TPA induced a differentiated phenotype that more closely resembled that of the monocyte-macrophage lineage. c-myc expression was down-regulated in K562 differentiated by both TPA and staurosporine, whereas max expression did not change in either case. Although PKC enzymatic activity was low in cells terminally differentiated with TPA and staurosporine, inhibition of PKC activity by itself did not induce c-myc down-regulation. We conclude that the c-myc gene is switched off as a consequence of the differentiation process triggered by these drugs in a manner independent from PKC. Ectopic overexpression of c-Myc in K562 cells did not affect the monocytic-macrophagic and megakaryocytic differentiation, indicating that c-Myc suppression is not required for these processes in K562. Similarly, both differentiation pathways were not affected by Max overexpression or by concomitant overexpression of c-Myc and Max. This result is in contrast with the inhibition of erythroid differentiation of K562 exerted by c-Myc, suggesting divergent roles for c-Myc/Max, depending on the differentiation pathway.

This article has been cited by other articles:

				P. G. Fuhrken, C. Chen, P. A. Apostolidis, M. Wang, W. M. Miller, and E. T. Papoutsakis Gene Ontology-driven transcriptional analysis of CD34+ cell-initiated megakaryocytic cultures identifies new transcriptional regulators of megakaryopoiesis Physiol Genomics, April 1, 2008; 33(2): 159 - 169. [Abstract] [Full Text] [PDF]

				C. A. Williams, D. Mondal, and K. C. Agrawal The HIV-1 Tat Protein Enhances Megakaryocytic Commitment of K562 Cells by Facilitating CREB Transcription Factor Coactivation by CBP Experimental Biology and Medicine, December 1, 2005; 230(11): 872 - 884. [Abstract] [Full Text] [PDF]

				K. Maki, T. Yamagata, T. Asai, I. Yamazaki, H. Oda, H. Hirai, and K. Mitani Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos Blood, September 15, 2005; 106(6): 2147 - 2155. [Abstract] [Full Text] [PDF]

				V. Torrano, I. Chernukhin, F. Docquier, V. D'Arcy, J. Leon, E. Klenova, and M. D. Delgado CTCF Regulates Growth and Erythroid Differentiation of Human Myeloid Leukemia Cells J. Biol. Chem., July 29, 2005; 280(30): 28152 - 28161. [Abstract] [Full Text] [PDF]

				Y.-W. Lin, C. Slape, Z. Zhang, and P. D. Aplan NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia Blood, July 1, 2005; 106(1): 287 - 295. [Abstract] [Full Text] [PDF]

				M. J. Munoz-Alonso, J. C. Acosta, C. Richard, M. D. Delgado, J. Sedivy, and J. Leon p21Cip1 and p27Kip1 Induce Distinct Cell Cycle Effects and Differentiation Programs in Myeloid Leukemia Cells J. Biol. Chem., May 6, 2005; 280(18): 18120 - 18129. [Abstract] [Full Text] [PDF]

				A. Kumar, C. M. Lee, and E. P. Reddy c-Myc Is Essential but Not Sufficient for c-Myb-mediated Block of Granulocytic Differentiation J. Biol. Chem., March 21, 2003; 278(13): 11480 - 11488. [Abstract] [Full Text] [PDF]