This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, S.-L.
Right arrow Articles by Mock, B. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, S.-L.
Right arrow Articles by Mock, B. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2001, p. 310-318, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.310-318.2001

Efficiency Alleles of the Pctr1 Modifier Locus for Plasmacytoma Susceptibility†

Shuling-L. Zhang,1 Wendy DuBois,1 Edward S. Ramsay,1 Valeri Bliskovski,1 Herbert C. Morse III,2 Leki Taddesse-Heath,2 William C. Vass,3 Ronald A. DePinho,4 and Beverly A. Mock1,*

Laboratory of Genetics1 and Laboratory of Cellular Oncology,3 Division of Basic Sciences, National Cancer Institute, and Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases,2 National Institutes of Health, Bethesda, Maryland 20892, and Department of Adult Oncology, Dana-Farber Cancer Institute, and Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts 021154

Received 10 August 2000/Accepted 27 September 2000

The susceptibility of BALB/c mice to pristane-induced plasmacytomas is a complex genetic trait involving multiple loci, while DBA/2 and C57BL/6 strains are genetically resistant to the plasmacytomagenic effects of pristane. In this model system for human B-cell neoplasia, one of the BALB/c susceptibility and modifier loci, Pctr1, was mapped to a 5.7-centimorgan (cM) chromosomal region that included Cdkn2a, which encodes p16INK4a and p19ARF, and the coding sequences for the BALB/c p16INK4a and p19ARF alleles were found to be polymorphic with respect to their resistant Pctr1 counterparts in DBA/2 and C57BL/6 mice (45). In the present study, alleles of Pctr1, Cdkn2a, and D4Mit15 from a resistant strain (BALB/cDAG) carrying DBA/2 chromatin were introgressively backcrossed to the susceptible BALB/c strain. The resultant C.DAG-Pctr1 Cdkn2a D4Mit15 congenic was more resistant to plasmacytomagenesis than BALB/c, thus narrowing Pctr1 to a 1.5-cM interval. Concomitantly, resistant C57BL/6 mice, from which both gene products of the Cdkn2a gene have been eliminated, developed pristane-induced plasma cell tumors over a shorter latency period than the traditionally susceptible BALB/cAn strain. Biological assays of the p16INK4a and p19ARF alleles from BALB/c and DBA/2 indicated that the BALB/c p16INK4a allele was less active than its DBA/2 counterpart in inducing growth arrest of mouse plasmacytoma cell lines and preventing ras-induced transformation of NIH 3T3 cells, while the two p19ARF alleles displayed similar potencies in both assays. We propose that the BALB/c susceptibility/modifier locus, Pctr1, is an "efficiency" allele of the p16INK4a gene.

* Corresponding author. Mailing address: Bldg. 37, Rm. 2B-08, 37 Convent Dr., MSC 4255, NCI, NIH, Bethesda, MD 20892-4255. Phone: (301) 496-2360 or (301) 496-3381. Fax: (301) 402-1031. E-mail: bev{at}helix.nih.gov.

dagger We dedicate this paper to the memory of Richard P. Nordan.

Molecular and Cellular Biology, January 2001, p. 310-318, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.310-318.2001


This article has been cited by other articles:

  • Zhang, K., Kagan, D., DuBois, W., Robinson, R., Bliskovsky, V., Vass, W. C., Zhang, S., Mock, B. A. (2009). Mndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth, and may modify plasmacytoma susceptibility. Blood 114: 2952-2960 [Abstract] [Full Text]  
  • Jawad, M, Giotopoulos, G, Cole, C, Plumb, M (2007). Target cell frequency is a genetically determined risk factor in radiation leukaemogenesis. Br. J. Radiol. 80: S56-S62 [Abstract] [Full Text]  
  • Dib, A., Barlogie, B., Shaughnessy, J. D. Jr, Kuehl, W. M. (2007). Methylation and expression of the p16INK4A tumor suppressor gene in multiple myeloma. Blood 109: 1337-1338 [Full Text]  
  • Hill, R., Song, Y., Cardiff, R. D., Van Dyke, T. (2005). Heterogeneous Tumor Evolution Initiated by Loss of pRb Function in a Preclinical Prostate Cancer Model. Cancer Res. 65: 10243-10254 [Abstract] [Full Text]  
  • Luo, H., Li, Q., O'Neal, J., Kreisel, F., Le Beau, M. M., Tomasson, M. H. (2005). c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood 106: 2452-2461 [Abstract] [Full Text]  
  • Park, S. S., Shaffer, A. L., Kim, J. S., duBois, W., Potter, M., Staudt, L. M., Janz, S. (2005). Insertion of Myc into Igh Accelerates Peritoneal Plasmacytomas in Mice. Cancer Res. 65: 7644-7652 [Abstract] [Full Text]  
  • Mock, B. A., Zhang, S., Ramsay, E. S., Bliskovsky, V., Zhang, K., Shi, W., DuBois, W. (2005). Strategies for Dissecting Complex Traits Associated with Cancer: Lessons from Plasma Cell Tumors. aacredbook 2005: 273-276 [Full Text]  
  • Matheu, A., Pantoja, C., Efeyan, A., Criado, L. M., Martin-Caballero, J., Flores, J. M., Klatt, P., Serrano, M. (2004). Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev. 18: 2736-2746 [Abstract] [Full Text]  
  • Bauer, A. K., Malkinson, A. M., Kleeberger, S. R. (2004). Susceptibility to neoplastic and non-neoplastic pulmonary diseases in mice: genetic similarities. Am. J. Physiol. Lung Cell. Mol. Physiol. 287: L685-L703 [Abstract] [Full Text]  
  • Felix, K., Gerstmeier, S., Kyriakopoulos, A., Howard, O. M. Z., Dong, H.-F., Eckhaus, M., Behne, D., Bornkamm, G. W., Janz, S. (2004). Selenium Deficiency Abrogates Inflammation-Dependent Plasma Cell Tumors in Mice. Cancer Res. 64: 2910-2917 [Abstract] [Full Text]  
  • Sachs, Z., Sharpless, N. E., DePinho, R. A., Rosenberg, N. (2004). p16Ink4a Interferes with Abelson Virus Transformation by Enhancing Apoptosis. J. Virol. 78: 3304-3311 [Abstract] [Full Text]  
  • Fonseca, R., Barlogie, B., Bataille, R., Bastard, C., Bergsagel, P. L., Chesi, M., Davies, F. E., Drach, J., Greipp, P. R., Kirsch, I. R., Kuehl, W. M., Hernandez, J. M., Minvielle, S., Pilarski, L. M., Shaughnessy, J. D. Jr., Stewart, A. K., Avet-Loiseau, H. (2004). Genetics and Cytogenetics of Multiple Myeloma: A Workshop Report. Cancer Res. 64: 1546-1558 [Abstract] [Full Text]  
  • Felix, K., Polack, A., Pretsch, W., Jackson, S. H., Feigenbaum, L., Bornkamm, G.-W., Janz, S. (2004). Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice. Cancer Res. 64: 530-537 [Abstract] [Full Text]  
  • Silva, S., Kovalchuk, A. L., Kim, J. S., Klein, G., Janz, S. (2003). BCL2 Accelerates Inflammation-induced BALB/c Plasmacytomas and Promotes Novel Tumors with Coexisting T(12;15) and T(6;15) Translocations. Cancer Res. 63: 8656-8663 [Abstract] [Full Text]  
  • Bliskovsky, V., Ramsay, E. S., Scott, J., DuBois, W., Shi, W., Zhang, S., Qian, X., Lowy, D. R., Mock, B. A. (2003). Frap, FKBP12 rapamycin-associated protein, is a candidate gene for the plasmacytoma resistance locus Pctr2 and can act as a tumor suppressor gene. Proc. Natl. Acad. Sci. USA 100: 14982-14987 [Abstract] [Full Text]  
  • Macdiarmid, J., Stevenson, D., Campbell, D. H., Wilson, J. B. (2003). The latent membrane protein 1 of Epstein-Barr virus and loss of the INK4a locus: paradoxes resolve to cooperation in carcinogenesis in vivo. Carcinogenesis 24: 1209-1218 [Abstract] [Full Text]  
  • Dragani, T. A. (2003). 10 Years of Mouse Cancer Modifier Loci: Human Relevance. Cancer Res. 63: 3011-3018 [Abstract] [Full Text]  
  • Blackburn, A. C., Brown, J. S., Naber, S. P., Otis, C. N., Wood, J. T., Jerry, D. J. (2003). BALB/c Alleles for Prkdc and Cdkn2a Interact to Modify Tumor Susceptibility in Trp53+/- Mice. Cancer Res. 63: 2364-2368 [Abstract] [Full Text]  
  • Bardeesy, N., Morgan, J., Sinha, M., Signoretti, S., Srivastava, S., Loda, M., Merlino, G., DePinho, R. A. (2002). Obligate Roles for p16Ink4a and p19Arf-p53 in the Suppression of Murine Pancreatic Neoplasia. Mol. Cell. Biol. 22: 635-643 [Abstract] [Full Text]  
  • Kovalchuk, A. L., Kim, J. S., Park, S. S., Coleman, A. E., Ward, J. M., Morse, H. C. III, Kishimoto, T., Potter, M., Janz, S. (2002). IL-6 transgenic mouse model for extraosseous plasmacytoma. Proc. Natl. Acad. Sci. USA 99: 1509-1514 [Abstract] [Full Text]  
  • Wei, Q., Adelstein, R. S. (2002). Pitx2a Expression Alters Actin-Myosin Cytoskeleton and Migration of HeLa Cells through Rho GTPase Signaling. Mol. Biol. Cell 13: 683-697 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»