| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology and Genetics |
Departments of Biochemistry [A. S., K. H.], Dermatology [T. I., M. M.], and Anatomy [H. S.], Akita University School of Medicine, Akita 010-8543, Japan; Department of Molecular Cell Biology, Research Institute for Microbial Disease [M. O., T. N.], Department of Dermatology [S. I.], and Department of Social and Environmental Medicine [N. K., J. T.], Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan [T. S.]; and Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario, M5G 2C1 Canada [T. W. M.]
PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate a keratinocyte-specific null mutation of Pten in mice (k5Ptenflox/flox mice). k5Ptenflox/flox mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in k5Ptenflox/flox mice. Within 3 weeks of birth, 90% of k5Ptenflox/flox mice die of malnutrition possibly caused by hyperkeratosis of the esophagus. All k5Ptenflox/flox mice develop spontaneous tumors within 8.5 months of birth, and chemical treatment accelerates the onset of tumors. k5Ptenflox/flox keratinocytes are hyperproliferative and resistant to apoptosis and show increased activation of the Pten downstream signaling mediators Akt/protein kinase B (PKB) and extracellular signal-regulated kinase. Pten is thus an important regulator of normal development and oncogenesis in the skin.
This article has been cited by other articles:
|
|
 |
|
  C. H. Squarize, R. M. Castilho, and J. S. Gutkind Chemoprevention and Treatment of Experimental Cowden's Disease by mTOR Inhibition with Rapamycin Cancer Res., September 1, 2008; 68(17): 7066 - 7072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Hu, Y. Liu, C. Zhang, Y. Zhao, W. He, L. Han, L. Yang, K. M. Hopkins, X. Yang, H. B. Lieberman, et al. Targeted Deletion of Rad9 in Mouse Skin Keratinocytes Enhances Genotoxin-Induced Tumor Development Cancer Res., July 15, 2008; 68(14): 5552 - 5561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yao, C. L. Alexander, J. A. Quinn, W.-C. Chan, H. Wu, and D. A. Greenhalgh Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21WAF-induced differentiation triggered by GSK3{beta} inactivation and reduced AKT activity J. Cell Sci., May 15, 2008; 121(10): 1758 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Segrelles, M. Moral, C. Lorz, M. Santos, J. Lu, J. L. Cascallana, M. F. Lara, S. Carbajal, A. B. Martinez-Cruz, R. Garcia-Escudero, et al. Constitutively Active Akt Induces Ectodermal Defects and Impaired Bone Morphogenetic Protein Signaling Mol. Biol. Cell, January 1, 2008; 19(1): 137 - 149. [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]
|
|
|
|
 |
|
 R. F. L. O'Shaughnessy, J. C. Welti, J. C. Cooke, A. A. Avilion, B. Monks, M. J. Birnbaum, and C. Byrne AKT-dependent HspB1 (Hsp27) Activity in Epidermal Differentiation J. Biol. Chem., June 8, 2007; 282(23): 17297 - 17305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, X. C. He, W.-G. Tong, T. Johnson, L. M. Wiedemann, Y. Mishina, J. Q. Feng, and L. Li Bone Morphogenetic Protein Signaling Inhibits Hair Follicle Anagen Induction by Restricting Epithelial Stem/Progenitor Cell Activation and Expansion Stem Cells, December 1, 2006; 24(12): 2826 - 2839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pankow, C. Bamberger, A. Klippel, and S. Werner Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase J. Cell Sci., October 1, 2006; 119(19): 4033 - 4046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsuruta, H. Kishimoto, T. Sasaki, Y. Horie, M. Natsui, Y. Shibata, K. Hamada, N. Yajima, K. Kawahara, M. Sasaki, et al. Hyperplasia and Carcinomas in Pten-Deficient Mice and Reduced PTEN Protein in Human Bladder Cancer Patients. Cancer Res., September 1, 2006; 66(17): 8389 - 8396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Teng, A.-N. Sun, X.-C. Pan, G. Yang, L.-L. Yang, M.-R. Wang, and X. Yang Synergistic Function of Smad4 and PTEN in Suppressing Forestomach Squamous Cell Carcinoma in the Mouse. Cancer Res., July 15, 2006; 66(14): 6972 - 6981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mahimainathan, F. Das, B. Venkatesan, and G. G. Choudhury Mesangial Cell Hypertrophy by High Glucose Is Mediated by Downregulation of the Tumor Suppressor PTEN. Diabetes, July 1, 2006; 55(7): 2115 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, Y. Hu, Y. Huo, M. Liu, D. Freeman, J. Gao, X. Liu, D.-C. Wu, and H. Wu PTEN Deletion Leads to Up-regulation of a Secreted Growth Factor Pleiotrophin J. Biol. Chem., April 21, 2006; 281(16): 10663 - 10668. [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]
|
|
|
|
|
|
D. Yao, C. L. Alexander, J. A. Quinn, M. J. Porter, H. Wu, and D. A. Greenhalgh PTEN Loss Promotes rasHa-Mediated Papillomatogenesis via Dual Up-Regulation of AKT Activity and Cell Cycle Deregulation but Malignant Conversion Proceeds via PTEN-Associated Pathways Cancer Res., February 1, 2006; 66(3): 1302 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ruiz, M. Santos, M. F. Lara, C. Segrelles, C. Ballestin, and J. M. Paramio Unexpected Roles for pRb in Mouse Skin Carcinogenesis Cancer Res., November 1, 2005; 65(21): 9678 - 9686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yang, C. Mao, Y. Teng, W. Li, J. Zhang, X. Cheng, X. Li, X. Han, Z. Xia, H. Deng, et al. Targeted Disruption of Smad4 in Mouse Epidermis Results in Failure of Hair Follicle Cycling and Formation of Skin Tumors Cancer Res., October 1, 2005; 65(19): 8671 - 8678. [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]
|
|
|
|
 |
|
 L. Ma, J. Teruya-Feldstein, N. Behrendt, Z. Chen, T. Noda, O. Hino, C. Cordon-Cardo, and P. P. Pandolfi Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression Genes & Dev., August 1, 2005; 19(15): 1779 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Yue, M. Groszer, J. S. Gil, A. J. Berk, A. Messing, H. Wu, and X. Liu PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization Development, July 15, 2005; 132(14): 3281 - 3291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. El-Abaseri, J. Fuhrman, C. Trempus, I. Shendrik, R. W. Tennant, and L. A. Hansen Chemoprevention of UV Light-Induced Skin Tumorigenesis by Inhibition of the Epidermal Growth Factor Receptor Cancer Res., May 1, 2005; 65(9): 3958 - 3965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kurlawalla-Martinez, B. Stiles, Y. Wang, S. U. Devaskar, B. B. Kahn, and H. Wu Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue Mol. Cell. Biol., March 15, 2005; 25(6): 2498 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Di-Poi, C. Y. Ng, N. S. Tan, Z. Yang, B. A. Hemmings, B. Desvergne, L. Michalik, and W. Wahli Epithelium-Mesenchyme Interactions Control the Activity of Peroxisome Proliferator-Activated Receptor {beta}/{delta} during Hair Follicle Development Mol. Cell. Biol., March 1, 2005; 25(5): 1696 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wijesekara, D. Konrad, M. Eweida, C. Jefferies, N. Liadis, A. Giacca, M. Crackower, A. Suzuki, T. W. Mak, C. R. Kahn, et al. Muscle-Specific Pten Deletion Protects against Insulin Resistance and Diabetes Mol. Cell. Biol., February 1, 2005; 25(3): 1135 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Fraser, X. Zhu, C.-H. Kwon, E. J. Uhlmann, D. H. Gutmann, and S. J. Baker Pten Loss Causes Hypertrophy and Increased Proliferation of Astrocytes In vivo Cancer Res., November 1, 2004; 64(21): 7773 - 7779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cully, A. Elia, S.-H. Ong, V. Stambolic, T. Pawson, M.-S. Tsao, and T. W. Mak grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in pten+/- mice PNAS, October 26, 2004; 101(43): 15358 - 15363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. McCormick, Y. Feng, K. Dawson, M. J. Behne, B. Yu, J. Wang, A. W. Wyatt, G. Henke, F. Grahammer, T. M. Mauro, et al. Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development Mol. Biol. Cell, September 1, 2004; 15(9): 4278 - 4288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Mao, M. D. To, J. Perez-Losada, D. Wu, R. Del Rosario, and A. Balmain Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression Genes & Dev., August 1, 2004; 18(15): 1800 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Segrelles, S. Ruiz, M. Santos, J. Martinez-Palacio, M. F. Lara, and J. M. Paramio Akt mediates an angiogenic switch in transformed keratinocytes Carcinogenesis, July 1, 2004; 25(7): 1137 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Backman, D. Ghazarian, K. So, O. Sanchez, K.-U. Wagner, L. Hennighausen, A. Suzuki, M.-S. Tsao, W. B. Chapman, V. Stambolic, et al. Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten PNAS, February 10, 2004; 101(6): 1725 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Ward and D. E. Devor-Henneman Mouse Models of Human Familial Cancer Syndromes Toxicol Pathol, January 1, 2004; 32(1_suppl): 90 - 98. [Abstract] [PDF]
|
|
|
|
|
|
C.-H. Kwon, X. Zhu, J. Zhang, and S. J. Baker mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo PNAS, October 28, 2003; 100(22): 12923 - 12928. [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 |
