Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print October 24, 2007
Mol. Biol. Cell 10.1091/mbc.E07-08-0764

A more recent version of this article appeared on January 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-08-0764v1
19/1/137    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Segrelles, C.
Right arrow Articles by Paramio, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Segrelles, C.
Right arrow Articles by Paramio, J. M.

Submitted on August 7, 2007
Revised on September 21, 2007
Accepted on October 17, 2007

Constitutively Active Akt Induces Ectodermal Defects and Impaired BMP Signaling

Carmen Segrelles,*{dagger} Marta Moral,*{dagger} Corina Lorz,*{dagger} Mirentxu Santos,* Jerry Lu,{ddagger} José Luis Cascallana,{sect} M. Fernanda Lara,* Steve Carbajal,{ddagger} Ana Belén Martínez-Cruz,* Ramón García-Escudero,* Linda Beltran,{ddagger} José C. Segovia,|| Ana Bravo,{sect} John DiGiovanni,{ddagger} and Jesús M. Paramio*

*Molecular Oncology Unit, Division of Biomedicine, CIEMAT, E-28040 Madrid, Spain; {ddagger}Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957; {sect}Department of Veterinary Clinical Sciences, Veterinary Pathology Unit, Veterinary Faculty, University of Santiago de Compostela, E-27002 Lugo, Spain; ||Flow Cytometry Unit, Division of Hematopoiesis, CIEMAT, E-28040 Madrid, Spain

Monitoring Editor: M. Bishr Omary

Aberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and noncell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1 (myrAkt) in transgenic mice. Contrary to mice overexpressing wild type Akt1 (Aktwt), these myrAkt mice display, in a dose-dependent manner, altered development of ectodermally derived organs such as hair, teeth, nails and epidermal glands. To identify the possible molecular mechanisms underlying these alterations, gene profiling approaches were used. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein (BMP)-dependent signaling pathway. In addition, these mice also display alterations in adult epidermal stem cells. Collectively, we show that epithelial tissue development and homeostasis is dependent on proper regulation of Akt expression and activity.

{dagger}These authors contributed equally to this work.

Address correspondence to: John DiGiovanni (jdigiovanni{at}mdanderson.org) or Jesús M. Paramio (jesusm.paramio{at}ciemat.es)




This article has been cited by other articles:


Home page
 In VivoHome page
M. MORAL, C. SEGRELLES, A. B. MARTINEZ-CRUZ, C. LORZ, M. SANTOS, R. GARCIA-ESCUDERO, J. LU, A. BUITRAGO, C. COSTA, C. SAIZ, et al.
Transgenic Mice Expressing Constitutively Active Akt in Oral Epithelium Validate KLFA as a Potential Biomarker of Head and Neck Squamous Cell Carcinoma
In Vivo, September 1, 2009; 23(5): 653 - 660.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Moral, C. Segrelles, M. F. Lara, A. B. Martinez-Cruz, C. Lorz, M. Santos, R. Garcia-Escudero, J. Lu, K. Kiguchi, A. Buitrago, et al.
Akt Activation Synergizes with Trp53 Loss in Oral Epithelium to Produce a Novel Mouse Model for Head and Neck Squamous Cell Carcinoma
Cancer Res., February 1, 2009; 69(3): 1099 - 1108.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.