The fully linked HTML version of this article has now been published.
Development ePress online publication date 3 Mar 2004
doi: 10.1242/dev.01038
Research article: Development and disease
Roles of p63 in the diethylstilbestrol-induced cervicovaginal adenosis
Takeshi Kurita*,
Alea A. Mills,
and
Gerald R. Cunha
* Author for correspondence (e-mail: kurita{at}itsa.ucsf.edu)
Women exposed to diethylstilbestrol (DES) in utero develop abnormalities, including cervicovaginal adenosis that can lead to cancer. We report that transient disruption of developmental signals by DES permanently changes expression of p63, thereby altering the developmental fate of Müllerian duct epithelium. The cell fate of Müllerian epithelium to be columnar (uterine) or squamous (cervicovaginal) is determined by mesenchymal induction during the perinatal period. Cervicovaginal mesenchyme induced p63 in Müllerian duct epithelium and subsequent squamous differentiation. In p63-/- mice, cervicovaginal epithelium differentiated into uterine epithelium. Thus, p63 is an identity switch for Müllerian duct epithelium to be cervicovaginal versus uterine. P63 was also essential for uterine squamous metaplasia induced by DES-exposure. DES-exposure from postnatal day 1 to 5 inhibited induction of p63 in cervicovaginal epithelium via epithelial ER
. The inhibitory effect of DES was transient, and most cervicovaginal epithelial cells recovered expression of p63 by 2 days after discontinuation of DES-treatment. However, some cervicovaginal epithelial cells failed to express p63, remained columnar and persisted into adulthood as adenosis.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
W. Cheng, W. B. Jacobs, J. J. R. Zhang, A. Moro, J.-H. Park, M. Kushida, W. Qiu, A. A. Mills, and P. C. W. Kim
{Delta}Np63 plays an anti-apoptotic role in ventral bladder development
Development,
December 1, 2006;
133(23):
4783 - 4792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yin, C. Lin, and L. Ma
Msx2 Promotes Vaginal Epithelial Differentiation and Wolffian Duct Regression and Dampens the Vaginal Response to Diethylstilbestrol
Mol. Endocrinol.,
July 1, 2006;
20(7):
1535 - 1546.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Keyes, H. Vogel, M. I. Koster, X. Guo, Y. Qi, K. M. Petherbridge, D. R. Roop, A. Bradley, and A. A. Mills
p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors
PNAS,
May 30, 2006;
103(22):
8435 - 8440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Keyes, Y. Wu, H. Vogel, X. Guo, S. W. Lowe, and A. A. Mills
p63 deficiency activates a program of cellular senescence and leads to accelerated aging
Genes & Dev.,
September 1, 2005;
19(17):
1986 - 1999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yin and L. Ma
Development of the Mammalian Female Reproductive Tract
J. Biochem.,
June 1, 2005;
137(6):
677 - 683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Atanassova, C. McKinnell, J. Fisher, and R. M Sharpe
Neonatal treatment of rats with diethylstilboestrol (DES) induces stromal-epithelial abnormalities of the vas deferens and cauda epididymis in adulthood following delayed basal cell development
Reproduction,
May 1, 2005;
129(5):
589 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-W. Huang, Y. Yin, Q. Bi, T.-C. Chiang, N. Garner, J. Vuoristo, J. A. McLachlan, and L. Ma
Developmental Diethylstilbestrol Exposure Alters Genetic Pathways of Uterine Cytodifferentiation
Mol. Endocrinol.,
March 1, 2005;
19(3):
669 - 682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kurita, R. T. Medina, A. A. Mills, and G. R. Cunha
Role of p63 and basal cells in the prostate
Development,
October 15, 2004;
131(20):
4955 - 4964.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
