Carcinogenesis, Vol. 21, No. 4, 817-821,
April 2000
© 2000 Oxford University Press
Short Communications |
Characterization of the murine p19ARF promoter CpG island and its methylation pattern in primary lymphomas
Laboratorio de Genética Molecular Humana, Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain,
1 Centro Nacional de Investigaciones Oncológicas Carlos III, Crta. Majadahonda-Pozuelo, km 2, 28220 Majadahonda, Madrid and Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, 28049 Madrid, Spain and
2 Department of Pathology and Kaplan Comprehensive Cancer Center, New York University, 550 First Avenue, New York, NY 10016, USA
The INK4a/ARF locus encodes two different proteins involved in cell cycle control. Both molecules, p16INK4a and p19ARF, inhibit cell cycle progression and have been shown to act as tumor suppressors in a variety of models. Their expression is controlled by separate promoters responding to different stimuli and they therefore show independent transcriptional regulation. We have cloned and characterized a 2.5 kb region upstream of the murine p19ARF gene to determine the role of DNA methylation in suppressing p19ARF transcription in a wide panel of murine primary T cell lymphomas. This region contains a DNA fragment with the characteristics of a CpG island similar to those described for the murine p16INK4a and p15INK4b genes. Expression of p19ARF is decreased in a significant number (20%) of the murine lymphomas analyzed. Overexpression of the p19ARF transcript is also frequent, suggesting alterations in molecules of the retinoblastoma or p53 pathways that are involved in p19ARF regulation. Although hypermethylation of the INK4a and INK4b promoters is frequently involved in murine lymphomas, the p19ARF CpG island is infrequently methylated in the murine primary lymphomas studied in this work. Since loss of p19ARF expression cannot be explained as the result of homozygous deletions or hypermethylation of the ARF gene, other regulatory mechanisms seem to be altered in these malignancies.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M.M. de Yzaguirre, J.S. Hernandez, P.F. Navarro, P.L. Nieva, M. Herranz, M.F. Fraga, M. Esteller, A. Juarranz, and J. Fernandez-Piqueras Epigenetic silencing of E- and N-cadherins in the stroma of mouse thymic lymphomas Carcinogenesis, May 1, 2006; 27(5): 1081 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lopez-Nieva, J. Santos, and J. Fernandez-Piqueras Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in {gamma}-radiation-induced mouse thymic lymphomas Carcinogenesis, July 1, 2004; 25(7): 1299 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Tam, T. R. Devereux, A. C. Patel, J. F. Foley, R. R. Maronpot, and T. E. Massey Perturbations of the Ink4a/Arf gene locus in aflatoxin B1-induced mouse lung tumors Carcinogenesis, January 1, 2003; 24(1): 121 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sotillo, J. F. Garcia, S. Ortega, J. Martin, P. Dubus, M. Barbacid, and M. Malumbres Invasive melanoma in Cdk4-targeted mice PNAS, October 16, 2001; (2001) 241338598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakamura, T. Sakaki, H. Hashimoto, H. Nakase, E. Ishida, K. Shimada, and N. Konishi Frequent Alterations of the p14ARF and p16INK4a Genes in Primary Central Nervous System Lymphomas Cancer Res., September 1, 2001; 61(17): 6335 - 6339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Serrano The INK4a/ARF locus in murine tumorigenesis Carcinogenesis, May 1, 2000; 21(5): 865 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sotillo, J. F. Garcia, S. Ortega, J. Martin, P. Dubus, M. Barbacid, and M. Malumbres Invasive melanoma in Cdk4-targeted mice PNAS, November 6, 2001; 98(23): 13312 - 13317. [Abstract] [Full Text] [PDF]
|
|