| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
1 Department of Carcinogenesis, The University of Texas, M. D. Anderson Cancer Center, Science Park–Research Division, Smithville, Texas, and 2 Department of Biochemistry and Molecular Biology, Louisiana State Univeristy, Health Sciences Center, School of Medicine in Shreveport and Feist-Weiller Cancer Center, Shreveport, Louisiana
In the present study, we have investigated the possible role of signal transducers and activators of transcription (STATs), particularly Stat3, in mouse skin tumor promotion and multistage carcinogenesis. Stat1, Stat3, and Stat5 were activated in mouse epidermis after treatment with different classes of tumor promoters, including 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid, and chrysarobin. In addition, Stat1, Stat3, and Stat5 were constitutively activated in skin tumors generated by the two-stage carcinogenesis regimen using 7,12-dimethylbenz(a)anthracene as initiator and TPA as promoter. Several approaches were used to examine the possible role of epidermal growth factor receptor (EGFR) in modulating Stat3 activity during tumor promotion. In primary cultures of mouse keratinocytes, addition of exogenous EGF led to activation of Stat3 as shown by an elevation in tyrosine phosphorylation and nuclear translocation. In epidermis of transgenic mice expressing transforming growth factor 
under control of the keratin 14 promoter, Stat3 was constitutively activated. Abrogation of EGFR function in mouse epidermis using an EGFR kinase inhibitor or by overexpressing a dominant negative form of EGFR led to a reduction in Stat3 activation in response to TPA treatment. Immunoprecipitation analyses using lysates from TPA-treated epidermis and skin papillomas showed enhanced interaction between the EGFR and Stat3. Finally, Stat3 deficiency in mouse epidermis significantly reduced the proliferative response after TPA treatment. Collectively, the current results suggest that Stat3 activation may be a critical event during mouse skin tumor promotion, possibly through regulation of keratinocyte proliferation. In addition, Stat3 activation in tumor promoter-treated epidermis and in skin papillomas may occur, at least in part, via interaction with and phosphorylation by the EGFR. Finally, constitutive activation of Stat3 in both papillomas and squamous cell carcinomas suggest a role in both the development of autonomous growth and the progression of epithelial tumors in mouse skin.
This article has been cited by other articles:
|
|
 |
|
  C.-P. Kung and N. Raab-Traub Epstein-Barr Virus Latent Membrane Protein 1 Induces Expression of the Epidermal Growth Factor Receptor through Effects on Bcl-3 and STAT3 J. Virol., June 1, 2008; 82(11): 5486 - 5493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kataoka, D. J. Kim, S. Carbajal, J. L. Clifford, and J. DiGiovanni Stage-specific disruption of Stat3 demonstrates a direct requirement during both the initiation and promotion stages of mouse skin tumorigenesis Carcinogenesis, June 1, 2008; 29(6): 1108 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Moore, S. Carbajal, L. Beltran, S. N. Perkins, S. Yakar, D. LeRoith, S. D. Hursting, and J. DiGiovanni Reduced Susceptibility to Two-Stage Skin Carcinogenesis in Mice with Low Circulating Insulin-Like Growth Factor I Levels Cancer Res., May 15, 2008; 68(10): 3680 - 3688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Dougherty, A. Sehdev, S. Cerda, R. Mustafi, N. Little, W. Yuan, S. Jagadeeswaran, A. Chumsangsri, J. Delgado, M. Tretiakova, et al. Epidermal Growth Factor Receptor Controls Flat Dysplastic Aberrant Crypt Foci Development and Colon Cancer Progression in the Rat Azoxymethane Model Clin. Cancer Res., April 15, 2008; 14(8): 2253 - 2262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lu, O. Rho, E. Wilker, L. Beltran, and J. DiGiovanni Activation of Epidermal Akt by Diverse Mouse Skin Tumor Promoters Mol. Cancer Res., December 1, 2007; 5(12): 1342 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-S. Lai, S. Li, C.-Y. Chai, C.-Y. Lo, C.-T. Ho, Y.-J. Wang, and M.-H. Pan Inhibitory effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice Carcinogenesis, December 1, 2007; 28(12): 2581 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Bauman, K. D. Eaton, and R. G. Martins Treatment of Recurrent Squamous Cell Carcinoma of the Skin With Cetuximab Arch Dermatol, July 1, 2007; 143(7): 889 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rittie, S. Kansra, S. W. Stoll, Y. Li, J. E. Gudjonsson, Y. Shao, L. E. Michael, G. J. Fisher, T. M. Johnson, and J. T. Elder Differential ErbB1 Signaling in Squamous Cell versus Basal Cell Carcinoma of the Skin Am. J. Pathol., June 1, 2007; 170(6): 2089 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Brennan, Y. Hu, S. Joubeh, Y. W. Choi, D. Whitaker-Menezes, T. O'Brien, J. Uitto, U. Rodeck, and M. G. Mahoney Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes J. Cell Sci., March 1, 2007; 120(5): 758 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Aziz, H. T. Manoharan, and A. K. Verma Protein Kinase C{varepsilon}, which Sensitizes Skin to Sun's UV Radiation-Induced Cutaneous Damage and Development of Squamous Cell Carcinomas, Associates with Stat3 Cancer Res., February 1, 2007; 67(3): 1385 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Li, C. Marshall, L. Mei, J. Gelfand, and J. T. Seykora Srcasm Corrects Fyn-induced Epidermal Hyperplasia by Kinase Down-regulation J. Biol. Chem., January 12, 2007; 282(2): 1161 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wen, J. Craig, P. W Dyce, and J. Li Cloning of porcine signal transducer and activator of transcription 3 cDNA and its expression in reproductive tissues. Reproduction, September 1, 2006; 132(3): 511 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Han, A. J. Demetris, D. B. Stolz, L. Xu, K. Lim, and T. Wu Modulation of Stat3 Activation by the Cytosolic Phospholipase A2{alpha} and Cyclooxygenase-2-controlled Prostaglandin E2 Signaling Pathway J. Biol. Chem., August 25, 2006; 281(34): 24831 - 24846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Alvarez, H. Greulich, W. R. Sellers, M. Meyerson, and D. A. Frank Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Res., March 15, 2006; 66(6): 3162 - 3168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Leslie, C. Lang, G. Devgan, J. Azare, M. Berishaj, W. Gerald, Y. B. Kim, K. Paz, J. E. Darnell, C. Albanese, et al. Cyclin d1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3. Cancer Res., March 1, 2006; 66(5): 2544 - 2552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gartsbein, A. Alt, K. Hashimoto, K. Nakajima, T. Kuroki, and T. Tennenbaum The role of protein kinase C {delta} activation and STAT3 Ser727 phosphorylation in insulin-induced keratinocyte proliferation J. Cell Sci., February 1, 2006; 119(3): 470 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sano, K. S. Chan, M. Kira, K. Kataoka, S. Takagi, M. Tarutani, S. Itami, K. Kiguchi, M. Yokoi, K. Sugasawa, et al. Signal Transducer and Activator of Transcription 3 Is a Key Regulator of Keratinocyte Survival and Proliferation following UV Irradiation Cancer Res., July 1, 2005; 65(13): 5720 - 5729. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
