Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol.

Abstract

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life. To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR. We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling. This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

• Authors: S Miyagawa, A Suzuki, Y Katsu, M Kobayashi, M Goto, H Handa, H Watanabe, T Iguchi
• Journal: Journal of molecular endocrinology (J Mol Endocrinol) Vol. 32 Issue 3 Pg. 663-77 (Jun 2004) ISSN: 0952-5041 [Print] England
• PMID: 15171707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Interleukin-1
• Proto-Oncogene Proteins
• Insulin-Like Growth Factor I
• Diethylstilbestrol
• AKT1 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Animals, Newborn
• Carcinogens (pharmacology)
• Cell Differentiation (drug effects)
• Cell Proliferation
• Diethylstilbestrol (pharmacology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Insulin-Like Growth Factor I (genetics, metabolism)
• Interleukin-1 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Oligonucleotide Array Sequence Analysis
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt
• Signal Transduction (physiology)
• Vagina (cytology, drug effects, physiology)