Roles of p63 in the diethylstilbestrol-induced cervicovaginal adenosis

Kurita, T., Mills, A. A., Cunha, G. R. (April 2004) Roles of p63 in the diethylstilbestrol-induced cervicovaginal adenosis. Development, 131 (7). pp. 1639-1649. ISSN 0950-1991

DOI: 10.1242/dev.01038


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 Mullerian duct epithelium. The cell fate of Mullerian epithelium to be columnar (uterine) or squamous (cervicovaginal) is determined by mesenchymal induction during the perinatal period. Cervicovaginal mesenchyme induced p63 in Mullerian duct epithelium and subsequent squamous differentiation. In p63(-/-) mice, cervicovaginal epithelium differentiated into uterine epithelium. Thus, p63 is an identity switch for Mullerian duct epithelium to be cervicovaginal versus uterine. P63 was also essential for uterine squamous metaplasia induced by DES-exposure. DES-exposure from postnatal day I to 5 inhibited induction of p63 in cervicovaginal epithelium via epithelial ERalpha. 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.

Item Type: Paper
Uncontrolled Keywords: columnar-squamous transformation mullerian duct endocrine disruptor uterus estrogen receptor alpha EPIDERMOLYSIS-BULLOSA SIMPLEX epidermilysis bullosa simplex FEMALE REPRODUCTIVE-TRACT female reproductive tract PROGESTERONE-RECEPTOR progesterone recepter PARACRINE REGULATION paracrine regulation HUMAN KERATIN-14 human keratin-14 P53 HOMOLOG homolog YOUNG-WOMEN young women estrogen MICE mice ABNORMALITIES abnormalities
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p63
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: CSHL Librarian
Date: April 2004
Date Deposited: 31 Jan 2012 17:17
Last Modified: 02 Feb 2017 20:02
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