help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miliani de Marval, P. L.
Right arrow Articles by Rodriguez-Puebla, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miliani de Marval, P. L.
Right arrow Articles by Rodriguez-Puebla, M. L.
(American Journal of Pathology. 2001;159:369-379.)
© 2001 American Society for Investigative Pathology

Animal Model

Transgenic Expression of Cyclin-Dependent Kinase 4 Results in Epidermal Hyperplasia, Hypertrophy, and Severe Dermal Fibrosis

Paula L. Miliani de Marval, Irma B. Gimenez-Conti, Margaret LaCava, Luis A. Martinez, Claudio J. Conti and Marcelo L. Rodriguez-Puebla

From the Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, Texas

In a previous report we have described the effects of expression of D-type cyclins in epithelial tissues of transgenic mice. To study the involvement of the D-type cyclin partner cyclin-dependent kinase 4 (CDK4) in epithelial growth and differentiation, transgenic mice were generated carrying the CDK4 gene under the control of a keratin 5 promoter. As expected, transgenic mice showed expression of CDK4 in the epidermal basal-cell layer. Epidermal proliferation increased dramatically and basal cell hyperplasia and hypertrophy were observed. The hyperproliferative phenotype of these transgenic mice was independent of D-type cyclin expression because no overexpression of these proteins was detected. CDK4 and CDK2 kinase activities increased in transgenic animals and were associated with elevated binding of p27Kip1 to CDK4. Expression of CDK4 in the epidermis results in an increased spinous layer compared with normal epidermis, and a mild hyperkeratosis in the cornified layer. In addition to epidermal changes, severe dermal fibrosis was observed and part of the subcutaneous adipose tissue was replaced by connective tissue. Also, abnormal expression of keratin 6 associated with the hyperproliferative phenotype was observed in transgenic epidermis. This model provides in vivo evidence for the role of CDK4 as a mediator of proliferation in epithelial cells independent of D-type cyclin expression.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
E. Macias, P. L. Miliani de Marval, A. De Siervi, C. J. Conti, A. M. Senderowicz, and M. L. Rodriguez-Puebla
CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development
Am. J. Pathol., August 1, 2008; 173(2): 526 - 535.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Macias, P. L. Miliani de Marval, A. Senderowicz, J. Cullen, and M. L. Rodriguez-Puebla
Expression of CDK4 or CDK2 in Mouse Oral Cavity Is Retained in Adult Pituitary with Distinct Effects on Tumorigenesis
Cancer Res., January 1, 2008; 68(1): 162 - 171.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Macias, Y. Kim, P. L. Miliani de Marval, A. Klein-Szanto, and M. L. Rodriguez-Puebla
Cdk2 Deficiency Decreases ras/CDK4-Dependent Malignant Progression, but Not myc-Induced Tumorigenesis
Cancer Res., October 15, 2007; 67(20): 9713 - 9720.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W.-M. Chien, S. Rabin, E. Macias, P. L. Miliani de Marval, K. Garrison, J. Orthel, M. Rodriguez-Puebla, and M. L. Fero
Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1.
PNAS, March 14, 2006; 103(11): 4122 - 4127.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. L. Miliani de Marval, E. Macias, R. Rounbehler, P. Sicinski, H. Kiyokawa, D. G. Johnson, C. J. Conti, and M. L. Rodriguez-Puebla
Lack of Cyclin-Dependent Kinase 4 Inhibits c-myc Tumorigenic Activities in Epithelial Tissues
Mol. Cell. Biol., September 1, 2004; 24(17): 7538 - 7547.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
L. Richard-Parpaillon, R. A. Cosgrove, C. Devine, A. E. Vernon, and A. Philpott
G1/S phase cyclin-dependent kinase overexpression perturbs early development and delays tissue-specific differentiation in Xenopus
Development, June 1, 2004; 131(11): 2577 - 2586.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. D. Yu, M. Becker-Hapak, E. L. Snyder, M. Vooijs, C. Denicourt, and S. F. Dowdy
Distinct and nonoverlapping roles for pRB and cyclin D:cyclin-dependent kinases 4/6 activity in melanocyte survival
PNAS, December 9, 2003; 100(25): 14881 - 14886.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. L. Rodriguez-Puebla, P. L. Miliani de Marval, M. LaCava, D. S. Moons, H. Kiyokawa, and C. J. Conti
cdk4 Deficiency Inhibits Skin Tumor Development but Does Not Affect Normal Keratinocyte Proliferation
Am. J. Pathol., August 1, 2002; 161(2): 405 - 411.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
F. Benavides, M. F. Starost, M. Flores, I. B. Gimenez-Conti, J.-L. Guenet, and C. J. Conti
Impaired Hair Follicle Morphogenesis and Cycling with Abnormal Epidermal Differentiation in nackt Mice, a Cathepsin L-Deficient Mutation
Am. J. Pathol., August 1, 2002; 161(2): 693 - 703.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the American Society for Investigative Pathology.