Control Transcripcional del Cáncer y Regulación del Ciclo Celular


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viñetaLínea de Investigación:

ONCOPROTEÍNA MYC EN DIFERENCIACIÓN CELULAR Y LEUCEMIA

MYC ONCOPROTEIN IN CELL DIFFERENTIAITON AND LEUKEMIA

IP: Javier León, Catedrático de Bioquímica y Biología Molecular

Lucía García, predoctoral
Ester Molina, predoctoral
M. Carmen Lafita, predoctoral
Rosa Blanco, técnico de laboratorio

viñetaResearch interests:

  • Roles of Myc oncoprotein and Myc network proteins (Max and Mxds) in cell differentiation, using  myeloid leukemia, pheochromocytoma and human embryonic stem cells as model systems
  • Myc functional and physical interactions with cell cycle inhibitors of the Kip family (p27, p21), Skp2 and Sin3
  • Myc involvement in chronic myeloid leukemia and effects in the response to Tyr-kinase inhibitors

viñetaFunding:

  • Red Cooperativa de Investigación en Cáncer. Grupo Regular. ISCIII-RETIC-RD06/0020/0017. IP: Javier León
  • Nuevas interacciones y funciones del oncogen MYC en el control de la diferenciación y transformación celular SAF2011-23796. IP: Javier León

 

viñetaPublications (last 7 years):

Delgado, M.D., Albajar, M., Gomez-Casares, M.T., Batlle, A., and León, J. MYC oncogene in myeloid neoplasias. Clin Trans Oncol, 15: 87-94  (2013) .PMID: 22911553


Gómez-Casares, M.T. García-Alegria, E., López-Jorge, C.E., Ferrándiz, N., Blanco, R., Alvarez, S., Vaqué, J.P., , Bretones, G., Caraballo, J.M., Sanchez-Bailón, P., Delgado, M.D., Martin-Perez, J., Cigudosa, J.C., and León, J. MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through down-regulation of p27KIP1 . Oncogene 32:2239- 2246 (2012) 

 

Muñoz-Alonso MJ, Ceballos L, Bretones G, Frade P, León J, Gandarillas A. MYC accelerates p21(CIP) -induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells. J Cell Physiol. 227: 2069–2078 (2012)  

 

Albajar, M., Gómez-Casares, M.T., Llorca, J., Mauleon, J., Vaqué, J.P., Acosta, J.C., Bermúdez, A., Donato, N., Delgado, M.D. and León, J.   MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib. Mol Cancer Res 9: 564-576 (2011)

 

Bretones, G., Acosta J.C:, Caraballo, J., Ferrandiz, N., Gómez-Casares, M.T., Albajar, M., Blanco, R., Ruiz, P., Hung, W-C., Albero, M.P., Perez-Roger, I. and León J. Skp2 oncogene is a direct Myc target gene and Myc downregulates p27kip1 through Skp2 in human leukemia cells. J Biol Chem.  286: 9815-25 (2011)

 

Delgado, M.D and León, J. Myc roles in hematopoiesis and leukemia. Genes &Cancer (2010) 1: 605616. Review

Ferrandiz, N, Caraballo, J. M., Albajar, M, Gomez-Casares, M.T., López-Jorge, C.E., Blanco, R., Delgado, M.D. and Leon, J. p21Cip1 confers resistance to imatinib in human chronic myeloid leukemia cells. Cancer Lett 292: 133-139 (2010).

León J, Ferrándiz, N, Acosta, JC, Delgado, MD. Inhibition of cell differentiation: a critical mechanism for MYC-mediated carcinogenesis? Cell Cycle 8: 1148-1157 (2009)

Marques-Garcia F, Ferrandiz N, Fernandez-Alonso R, Gonzalez-Cano L, Herreros-Villanueva M, Rosa-Garrido M, Fernandez-Garcia B, Vaque JP, Marques MM, Alonso ME, Segovia JC, Leon J, Marin MC. p73 plays a role in erythroid differentiation through GATA1 induction. J Biol Chem. 284: 21139-21156 (2009)

Ferrandiz, N., Martin-Perez, J., Blanco, R, Donertas, D, Weber, A, Eilers, M, Dotto, P, Delgado, M.D. and Leon, J. HCT116 cells deficient in p21Waf1 are hypersensitive to tyrosine kinase inhibitors and adriamycin through a mechanism unrelated to p21 and dependent on p53. DNA Repair 8: 390-399 (2009).

López C, Ajenjo N, Muñoz-Alonso MJ, Frade P, León J, Gómez-Cimiano J. Determination of viability of human cartilage allografts by a rapid and quantitative method not requiring cartilage digestion. Cell Transplant. 17:859-64 (2008).

Acosta, J. C., Ferrándiz, N., Bretones, G., Blanco.,R., Torrano, V., Richard,C., OConell, B., Sedivy, J., Delgado, M.D.,  León, J. Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing the p27-mediated cell cycle arrest. Mol Cell Biol 28: 7286-7295 (2008).

Parreño,M., Casanova, I.,Céspedes, M.V., Vaqué, J.P.,Pavón,M.A., Leon, J. and Mangues, R.Bobel-24 and derivatives induce caspase-Independent Death in Pancreatic Cancer, regardless of Apoptotic Resistance. Cancer Res 68:6313-23 (2008).

Albajar, M. Gutierrez, P.,  Richard, C., Rosa-Garrido, M., Gómez-Casares, M.T., Steegmann, J.L. León, J. and Delgado M. D. PU.1 expression is restored upon treatment of chronic myeloid leukemia patients. Cancer Lett 270, 328-336 (2008).

Vaqué, JP., Fernández-García, B, García-Sanz, P., Ferrandiz, N., Bretones, G., Calvo, F., Crespo, P., Marín, M.C. and León, J. C-Myc inhibits Ras-mediated differentiation of pheochromocytoma cells by blocking c-Jun up-regulation. Mol Cancer Res. 6:325-339 (2008).

Renaud, S; Pugacheva, E; Delgado, M. D; Braunschweig, R; Abdullaev, Z; Loukinov, D Benhattar, J; Lobanenkov, V. Expression of the CTCF-paralogous Cancer-Testis Gene, Brother Of the Regulator of Imprinted Sites (BORIS), Is Regulated by Three Alternative Promoters Modulated by CpG-methylation and by CTCF and p53 Transcription Factors. Nuc Acids Res 35: 7372–7388 (2007).

Fernandez-Garcia, B., Vaqué, J.P., Herreros-Villanueva, M., F Marques-Garcia1, Castrillo, F., Fernandez-Medarde, A.,  León, J. and Marín, M.C. p73 cooperates with Ras in the activation of MAP kinase signaling cascade. Cell Death Diff. 14:254-265 (2007).

Delgado, M.D. and León, J. “Gene expression regulation and cancer”. Clinical & Translational Oncology 8:780-787 (2006).

Parreño, M., Vaqué, J.P., Casanova, I., Frade, P, Céspedes, M.V., Pavón, M.A., Molins, A., Camacho, M.,  Vila, L.,  Nomdedeu, J.F.,  Mangues, R., and León, J. Novel triiodo-phenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells which is inhibited by Myc. Mol. Cancer Ther. 5:1166-1175 (2006).

Torrano, V., Navascués, J., Docquier,F., Zhang, R., Burke, L., Chernukhin,I., Farrar, D., León, J., Berciano, M.T., Renkawitz, R., Klenova, E., Lafarga, M. and Delgado, M.D.  Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism. J. Cell Science. 119:1746-1759 (2006).

Torrano,V.,Chernukhin, I., Docquier, F., D’Arcy, V., Leon, J., Klenova, E., and Delgado, M.D. CTCF regulates growth and erythroid differentiation of human myeloid leukemia cells. J.Biol. Chem..280: 28152-28161 (2005).

Ceballos, E., Muñoz-Alonso, M.J., Berwanger, B, Acosta, J.C., Hernández, R., Krause, M., Hartman, O., Eilers, M. and León, J. Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and up-regulation of  chaperone genes. Oncogene 24: 4559-4571 (2005).

Muñoz-Alonso, M.J., Acosta, J.C., Richard, C., Delgado, M.D., Sedivy, J. and LeónJ. p21cip1 and p27kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells. J.  Biol. Chem. 280: 18120-18129 (2005).

Vaqué, J.P., Navascués, J., Shiio, Y., Laiho, M., Ajenjo, N., Mauleon, I., Matallanas, D., Crespo, P. and León, J. Myc antagonizes Ras-mediated growth arrest in leukemia cells through the inhibition of the Ras-Erk-p21Cip1 pathway. J.Biol. Chem. 280: 1112-1122 (2005).

 

viñetaContact:

Dr. Javier León

Phone: (+34) 942 201952 / Fax : (+34) 942 266399

Email: leonj@unican.es

Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander

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