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
Services
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 Pierce, A. M.
Right arrow Articles by Johnson, D. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pierce, A. M.
Right arrow Articles by Johnson, D. G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 1999, p. 6408-6414, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

E2F1 Has Both Oncogenic and Tumor-Suppressive Properties in a Transgenic Model

Angela M. Pierce, Robin Schneider-Broussard, Irma B. Gimenez-Conti, Jamie L. Russell, Claudio J. Conti, and David G. Johnson*

Department of Carcinogenesis, Science Park-Research Division, The University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957

Received 22 March 1999/Returned for modification 17 May 1999/Accepted 16 June 1999

Using a transgenic mouse model expressing the E2F1 gene under the control of a keratin 5 (K5) promoter, we previously demonstrated that increased E2F1 activity can promote tumorigenesis by cooperating with either a v-Ha-ras transgene to induce benign skin papillomas or p53 deficiency to induce spontaneous skin carcinomas. We now report that as K5 E2F1 transgenic mice age, they are predisposed to develop spontaneous tumors in a variety of K5-expressing tissues, including the skin, vagina, forestomach, and odontogenic epithelium. On the other hand, K5 E2F1 transgenic mice are found to be resistant to skin tumor development following a two-stage carcinogenesis protocol. Additional experiments suggest that this tumor-suppressive effect of E2F1 occurs at the promotion stage and may involve the induction of apoptosis. These findings demonstrate that increased E2F1 activity can either promote or inhibit tumorigenesis, dependent upon the experimental context.

* Corresponding author. Mailing address: Science Park-Research Division, The University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville, TX 78957. Phone: (512) 237-9511. Fax: (512) 237-2437. E-mail: djohnson{at}sprd1.mdacc.tmc.edu.

Molecular and Cellular Biology, September 1999, p. 6408-6414, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Garneau, H., Alvarez, L., Paquin, M.-C., Lussier, C., Rancourt, C., Tremblay, E., Beaulieu, J.-F., Rivard, N. (2007). Nuclear expression of E2F4 induces cell death via multiple pathways in normal human intestinal epithelial crypt cells but not in colon cancer cells. Am. J. Physiol. Gastrointest. Liver Physiol. 293: G758-G772 [Abstract] [Full Text]  
  • Qiao, H., Di Stefano, L., Tian, C., Li, Y.-Y., Yin, Y.-H., Qian, X.-P., Pang, X.-W., Li, Y., McNutt, M. A., Helin, K., Zhang, Y., Chen, W.-F. (2007). Human TFDP3, a Novel DP Protein, Inhibits DNA Binding and Transactivation by E2F. J. Biol. Chem. 282: 454-466 [Abstract] [Full Text]  
  • Davis, J. N., Wojno, K. J., Daignault, S., Hofer, M. D., Kuefer, R., Rubin, M. A., Day, M. L. (2006). Elevated E2F1 Inhibits Transcription of the Androgen Receptor in Metastatic Hormone-Resistant Prostate Cancer. Cancer Res. 66: 11897-11906 [Abstract] [Full Text]  
  • DeGregori, J. (2006). Surprising Dependency for Retinoblastoma Protein in Ras-Mediated Tumorigenesis. Mol. Cell. Biol. 26: 1165-1169 [Full Text]  
  • Alonso, M. M., Fueyo, J., Shay, J. W., Aldape, K. D., Jiang, H., Lee, O.-H., Johnson, D. G., Xu, J., Kondo, Y., Kanzawa, T., Kyo, S., Bekele, B. N., Zhou, X., Nigro, J., McDonald, J. M., Yung, W. K. A., Gomez-Manzano, C. (2005). Expression of Transcription Factor E2F1 and Telomerase in Glioblastomas: Mechanistic Linkage and Prognostic Significance. JNCI J Natl Cancer Inst 97: 1589-1600 [Abstract] [Full Text]  
  • Ruiz, S., Santos, M., Lara, M. F., Segrelles, C., Ballestin, C., Paramio, J. M. (2005). Unexpected Roles for pRb in Mouse Skin Carcinogenesis. Cancer Res. 65: 9678-9686 [Abstract] [Full Text]  
  • Rottmann, S., Wang, Y., Nasoff, M., Deveraux, Q. L., Quon, K. C. (2005). From the Cover: A TRAIL receptor-dependent synthetic lethal relationship between MYC activation and GSK3{beta}/FBW7 loss of function. Proc. Natl. Acad. Sci. USA 102: 15195-15200 [Abstract] [Full Text]  
  • Yamazaki, K, Hasegawa, M, Ohoka, I, Hanami, K, Asoh, A, Nagao, T, Sugano, I, Ishida, Y (2005). Increased E2F-1 expression via tumour cell proliferation and decreased apoptosis are correlated with adverse prognosis in patients with squamous cell carcinoma of the oesophagus. J. Clin. Pathol. 58: 904-910 [Abstract] [Full Text]  
  • Marques, M. R., Horner, J. S., Ihrie, R. A., Bronson, R. T., Attardi, L. D. (2005). Mice Lacking the p53/p63 Target Gene Perp Are Resistant to Papilloma Development. Cancer Res. 65: 6551-6556 [Abstract] [Full Text]  
  • Davis, J. N., McCabe, M. T., Hayward, S. W., Park, J. M., Day, M. L. (2005). Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells. Cancer Res. 65: 3633-3642 [Abstract] [Full Text]  
  • Scheijen, B., Bronk, M., van der Meer, T., De Jong, D., Bernards, R. (2004). High Incidence of Thymic Epithelial Tumors in E2F2 Transgenic Mice. J. Biol. Chem. 279: 10476-10483 [Abstract] [Full Text]  
  • Shen, W. H., Yin, Y., Broussard, S. R., McCusker, R. H., Freund, G. G., Dantzer, R., Kelley, K. W. (2004). Tumor Necrosis Factor {alpha} Inhibits Cyclin A Expression and Retinoblastoma Hyperphosphorylation Triggered by Insulin-like Growth Factor-I Induction of New E2F-1 Synthesis. J. Biol. Chem. 279: 7438-7446 [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]  
  • Wong, C. F., Barnes, L. M., Dahler, A. L., Smith, L., Serewko-Auret, M. M., Popa, C., Abdul-Jabbar, I., Saunders, N. A. (2003). E2F Modulates Keratinocyte Squamous Differentiation: IMPLICATIONS FOR E2F INHIBITION IN SQUAMOUS CELL CARCINOMA. J. Biol. Chem. 278: 28516-28522 [Abstract] [Full Text]  
  • Fong, L. Y. Y., Feith, D. J., Pegg, A. E. (2003). Antizyme Overexpression in Transgenic Mice Reduces Cell Proliferation, Increases Apoptosis, and Reduces N-Nitrosomethylbenzylamine-induced Forestomach Carcinogenesis. Cancer Res. 63: 3945-3954 [Abstract] [Full Text]  
  • Ngwenya, S., Safe, S. (2003). Cell Context-Dependent Differences in the Induction of E2F-1 Gene Expression by 17{beta}-Estradiol in MCF-7 and ZR-75 Cells. Endocrinology 144: 1675-1685 [Abstract] [Full Text]  
  • Ma, Y., Cress, W. D., Haura, E. B. (2003). Flavopiridol-induced Apoptosis Is Mediated through Up-Regulation of E2F1 and Repression of Mcl-1. Molecular Cancer Therapeutics 2: 73-81 [Abstract] [Full Text]  
  • Lindner, D. J., Ma, X., Hu, J., Karra, S., Kalvakolanu, D. V. (2002). Thioredoxin Reductase Plays a Critical Role in IFN Retinoid-mediated Tumor-Growth Control in Vivo. Clin. Cancer Res. 8: 3210-3218 [Abstract] [Full Text]  
  • Rounbehler, R. J., Rogers, P. M., Conti, C. J., Johnson, D. G. (2002). Inactivation of E2f1 Enhances Tumorigenesis in a Myc Transgenic Model. Cancer Res. 62: 3276-3281 [Abstract] [Full Text]  
  • Russell, J. L., Powers, J. T., Rounbehler, R. J., Rogers, P. M., Conti, C. J., Johnson, D. G. (2002). ARF Differentially Modulates Apoptosis Induced by E2F1 and Myc. Mol. Cell. Biol. 22: 1360-1368 [Abstract] [Full Text]  
  • Nicot, C., Harrod, R. (2000). Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein. Mol. Cell. Biol. 20: 8580-8589 [Abstract] [Full Text]  
  • Wang, D., Russell, J. L., Johnson, D. G. (2000). E2F4 and E2F1 Have Similar Proliferative Properties but Different Apoptotic and Oncogenic Properties In Vivo. Mol. Cell. Biol. 20: 3417-3424 [Abstract] [Full Text]  
  • DiGiovanni, J., Kiguchi, K., Frijhoff, A., Wilker, E., Bol, D. K., Beltran, L., Moats, S., Ramirez, A., Jorcano, J., Conti, C. (2000). Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc. Natl. Acad. Sci. USA 97: 3455-3460 [Abstract] [Full Text]  
  • Wang, A., Schneider-Broussard, R., Kumar, A. P., MacLeod, M. C., Johnson, D. G. (2000). Regulation of BRCA1 Expression by the Rb-E2F Pathway. J. Biol. Chem. 275: 4532-4536 [Abstract] [Full Text]  
  • Paramio, J. M., Segrelles, C., Casanova, M. L., Jorcano, J. L. (2000). Opposite Functions for E2F1 and E2F4 in Human Epidermal Keratinocyte Differentiation. J. Biol. Chem. 275: 41219-41226 [Abstract] [Full Text]  
  • Jiang, Z., Zacksenhaus, E. (2002). Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. JCB 156: 185-198 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»