| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Carcinogenesis |
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957 [J. D., D. K. B., E. W., L. B., S. C., S. M., K. K.], and Department of Cell and Molecular Biology, Ciemat Instituto, 28040 Madrid, Spain [A. R., J. J.]
Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in
the basal layer of skin epidermis were generated using the bovine
keratin 5 promoter (BK5). Neonatal transgenic mice were slightly
smaller at birth and exhibited early ear unfolding, wrinkled and
thickened skin, and slightly enlarged ears compared with nontransgenic
littermates. Morphological evaluation of the skin revealed that
persistent overexpression of IGF-1 in the basal layer of the epidermis
resulted in epidermal hyperplasia, hyperkeratosis, and an increased
labeling index that persisted in adult mice. Phenotypic changes
observed in skin were associated with transgene expression in the basal
layer of the epidermis and activation of the IGF-1 receptor. Squamous
papillomas (some of which converted to carcinomas) developed in a
significant proportion (
50%) of older BK5.IGF-1 mice. Treatment of
BK5.IGF-1 transgenic mice with multiple topical applications of the
phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, in
the absence of tumor initiation led to the development of additional
skin papillomas. Furthermore, treatment of BK5.IGF-1 transgenic mice
with an initiating dose of
7,12-dimethylbenz[a]anthracene only led to the
formation of additional papillomas in the absence of promotion. In
two-stage carcinogenesis experiments, BK5.IGF-1 transgenic mice
developed 7-fold more papillomas than nontransgenic littermates.
Phosphatidylinositol-3-kinase and protein kinase B (Akt) activities
were elevated (3–4-fold), and mitogen-activated protein kinase
activity was elevated 1.7-fold in the epidermis of transgenic mice
compared with nontransgenic mice. In addition, UV light-induced
epidermal apoptosis was significantly suppressed in BK5.IGF-1
transgenic mice. These data suggest that persistent activation of IGF-1
receptor signaling pathways in basal epithelial cells leads to
spontaneous tumor promotion and that up-regulation of both mitogenic
and cell survival signaling pathways may play an important role in the
action of IGF-1 in this model system.
This article has been cited by other articles:
|
|
 |
|
  W.-Y. Kim, Q. Jin, S.-H. Oh, E. S. Kim, Y. J. Yang, D. H. Lee, L. Feng, C. Behrens, L. Prudkin, Y. E. Miller, et al. Elevated Epithelial Insulin-like Growth Factor Expression Is a Risk Factor for Lung Cancer Development Cancer Res., September 15, 2009; 69(18): 7439 - 7448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.U. Lukacs, D.A. Lawson, L. Xin, Y. Zong, I. Garraway, A.S. Goldstein, S. Memarzadeh, and O.N. Witte Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.012v1. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Semenova, H. Koegel, S. Hasse, J. E. Klatte, E. Slonimsky, D. Bilbao, R. Paus, S. Werner, and N. Rosenthal Overexpression of mIGF-1 in Keratinocytes Improves Wound Healing and Accelerates Hair Follicle Formation and Cycling in Mice Am. J. Pathol., November 1, 2008; 173(5): 1295 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. de Ostrovich, I. Lambertz, J. K. L. Colby, J. Tian, J. E. Rundhaug, D. Johnston, C. J. Conti, J. DiGiovanni, and R. Fuchs-Young Paracrine Overexpression of Insulin-Like Growth Factor-1 Enhances Mammary Tumorigenesis in Vivo Am. J. Pathol., September 1, 2008; 173(3): 824 - 834. [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, L. Beltran, S. Carbajal, S. Strom, J. Traag, S. D. Hursting, and J. DiGiovanni Dietary Energy Balance Modulates Signaling through the Akt/Mammalian Target of Rapamycin Pathways in Multiple Epithelial Tissues Cancer Prevention Research, June 1, 2008; 1(1): 65 - 76. [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]
|
|
|
|
|
|
B. W. Sutherland, S. E. Knoblaugh, P. J. Kaplan-Lefko, F. Wang, M. Holzenberger, and N. M. Greenberg Conditional Deletion of Insulin-like Growth Factor-I Receptor in Prostate Epithelium Cancer Res., May 1, 2008; 68(9): 3495 - 3504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Martinez-Cruz, M. Santos, M. F. Lara, C. Segrelles, S. Ruiz, M. Moral, C. Lorz, R. Garcia-Escudero, and J. M. Paramio Spontaneous Squamous Cell Carcinoma Induced by the Somatic Inactivation of Retinoblastoma and Trp53 Tumor Suppressors Cancer Res., February 1, 2008; 68(3): 683 - 692. [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. Segrelles, J. Lu, B. Hammann, M. Santos, M. Moral, J. L. Cascallana, M. F. Lara, O. Rho, S. Carbajal, J. Traag, et al. Deregulated Activity of Akt in Epithelial Basal Cells Induces Spontaneous Tumors and Heightened Sensitivity to Skin Carcinogenesis Cancer Res., November 15, 2007; 67(22): 10879 - 10888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ablamunits, Y. Cohen, I. B. Brazee, H. P. Gaetz, C. Vinson, and S. Klebanov Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice. Cancer Res., September 1, 2006; 66(17): 8897 - 8902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, G. Chakravarty, S. Kim, Y. D. Yazici, M. N. Younes, S. A. Jasser, A. A. Santillan, C. D. Bucana, A. K. El-Naggar, and J. N. Myers Growth-Inhibitory Effects of Human Anti-Insulin-Like Growth Factor-I Receptor Antibody (A12) in an Orthotopic Nude Mouse Model of Anaplastic Thyroid Carcinoma Clin. Cancer Res., August 1, 2006; 12(15): 4755 - 4765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sadagurski, S. Yakar, G. Weingarten, M. Holzenberger, C. J. Rhodes, D. Breitkreutz, D. LeRoith, and E. Wertheimer Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation. Mol. Cell. Biol., April 1, 2006; 26(7): 2675 - 2687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, K. Sampat, N. Hu, J. Zakari, and S. H. Yuspa Protein Kinase C Negatively Regulates Akt Activity and Modifies UVC-induced Apoptosis in Mouse Keratinocytes J. Biol. Chem., February 10, 2006; 281(6): 3237 - 3243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. He, Y. M. Sung, J. DiGiovanni, and S. M. Fischer Thiazolidinediones Inhibit Insulin-Like Growth Factor-I-Induced Activation of p70S6 Kinase and Suppress Insulin-Like Growth Factor-I Tumor-Promoting Activity Cancer Res., February 1, 2006; 66(3): 1873 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Lamb and L. Zhang Challenges in Prostate Cancer Research: Animal Models for Nutritional Studies of Chemoprevention and Disease Progression J. Nutr., December 1, 2005; 135(12): 3009S - 3015S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Alonso, H. Okada, H. A. Pasolli, A. Wakeham, A. I. You-Ten, T. W. Mak, and E. Fuchs Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle J. Cell Biol., August 15, 2005; 170(4): 559 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Bassi, R. Lopez De Cicco, J. Cenna, S. Litwin, E. Cukierman, and A. J.P. Klein-Szanto PACE4 Expression in Mouse Basal Keratinocytes Results in Basement Membrane Disruption and Acceleration of Tumor Progression Cancer Res., August 15, 2005; 65(16): 7310 - 7319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Carboni, A. V. Lee, D. L. Hadsell, B. R. Rowley, F. Y. Lee, D. K. Bol, A. E. Camuso, M. Gottardis, A. F. Greer, C. P. Ho, et al. Tumor Development by Transgenic Expression of a Constitutively Active Insulin-Like Growth Factor I Receptor Cancer Res., May 1, 2005; 65(9): 3781 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Feith, D. K. Bol, J. M. Carboni, M. J. Lynch, S. Sass-Kuhn, P. L. Shoop, and L. M. Shantz Induction of Ornithine Decarboxylase Activity Is a Necessary Step for Mitogen-Activated Protein Kinase Kinase-Induced Skin Tumorigenesis Cancer Res., January 15, 2005; 65(2): 572 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shen, M. D. Person, J. Zhu, J. L. Abbruzzese, and D. Li Protein Expression Profiles in Pancreatic Adenocarcinoma Compared with Normal Pancreatic Tissue and Tissue Affected by Pancreatitis as Detected by Two-Dimensional Gel Electrophoresis and Mass Spectrometry Cancer Res., December 15, 2004; 64(24): 9018 - 9026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Patel, N. P. Nunez, S. N. Perkins, J. C. Barrett, and S. D. Hursting Effects of Energy Balance on Cancer in Genetically Altered Mice J. Nutr., December 1, 2004; 134(12): 3394S - 3398S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Endocr. Rev., December 1, 2003; 24(6): 737 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Suzuki, S. Itami, M. Ohishi, K. Hamada, T. Inoue, N. Komazawa, H. Senoo, T. Sasaki, J. Takeda, M. Manabe, et al. Keratinocyte-specific Pten Deficiency Results in Epidermal Hyperplasia, Accelerated Hair Follicle Morphogenesis and Tumor Formation Cancer Res., February 1, 2003; 63(3): 674 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Schmitz, R. L. Ahmed, and D. Yee Effects of a 9-Month Strength Training Intervention on Insulin, Insulin-like Growth Factor (IGF)-I, IGF-binding Protein (IGFBP)-1, and IGFBP-3 in 30-50-Year-Old Women Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1597 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Hsi, L. C. Wilson, and T. E. Eling Opposing Effects of 15-Lipoxygenase-1 and -2 Metabolites on MAPK Signaling in Prostate. ALTERATION IN PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR gamma J. Biol. Chem., October 18, 2002; 277(43): 40549 - 40556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Decraene, P. Agostinis, R. Bouillon, H. Degreef, and M. Garmyn Insulin-like Growth Factor-1-mediated AKT Activation Postpones the Onset of Ultraviolet B-induced Apoptosis, Providing More Time for Cyclobutane Thymine Dimer Removal in Primary Human Keratinocytes J. Biol. Chem., August 30, 2002; 277(36): 32587 - 32595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Santos, J. M. Paramio, A. Bravo, A. Ramirez, and J. L. Jorcano The Expression of Keratin K10 in the Basal Layer of the Epidermis Inhibits Cell Proliferation and Prevents Skin Tumorigenesis J. Biol. Chem., May 17, 2002; 277(21): 19122 - 19130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Satyamoorthy, G. Li, B. Vaidya, J. Kalabis, and M. Herlyn Insulin-like Growth Factor-I-induced Migration of Melanoma Cells Is Mediated by Interleukin-8 Induction Cell Growth Differ., February 1, 2002; 13(2): 87 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Satyamoorthy, G. Li, B. Vaidya, D. Patel, and M. Herlyn Insulin-like Growth Factor-1 Induces Survival and Growth of Biologically Early Melanoma Cells through Both the Mitogen-activated Protein Kinase and {beta}-Catenin Pathways Cancer Res., October 1, 2001; 61(19): 7318 - 7324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. LARCHER, M. DEL RIO, F. SERRANO, J. C. SEGOVIA, A. RAMIREZ, A. MEANA, A. PAGE, J. L. ABAD, M. A. GONZALEZ, J. BUEREN, et al. A cutaneous gene therapy approach to human leptin deficiencies: correction of the murine ob/ob phenotype using leptin-targeted keratinocyte grafts FASEB J, July 1, 2001; 15(9): 1529 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Masumori, T. Z. Thomas, P. Chaurand, T. Case, M. Paul, S. Kasper, R. M. Caprioli, T. Tsukamoto, S. B. Shappell, and R. J. Matusik A Probasin-Large T Antigen Transgenic Mouse Line Develops Prostate Adenocarcinoma and Neuroendocrine Carcinoma with Metastatic Potential Cancer Res., March 1, 2001; 61(5): 2239 - 2249. [Abstract] [Full Text]
|
|
| 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 |
