Keratinocyte growth factor causes cystic dilation of the mammary glands of mice: Interactions of keratinocyte growth factor, estrogen, and progesterone in vivo

Eunhee S. Yi, Adriana A. Bedoya, Hyesun Lee, Seokhyun Kim, Regina M. Housley, Sharon L. Aukerman, John E. Tarpley, Charles Starnes, Songmei Yin, Glenn F. Pierce, Thomas R. Ulich

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Abstract

Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell proliferation that has been reported to induce marked proliferation of mammary epithelium in rats. In this study, systemic administration of KGF into naive and oophorectomized mice causes mammary gland proliferation, as evidenced histologically by the appearance of cysts lined by a single layer of epithelium and by hyperplastic epithelium. Whole mount preparations of the mammary glands reveal that the histologically noted cysts are actually ducts that are dilated along much of their length. The histology of the mammary glands of KGF-treated mice is similar to the histology of fibrocystic disease in the human female breast. The response in mice differs significantly from the appearance of the mammary glands in KGF-treated rats in which ductal epithelial proliferation is most prominent. Estrogen and progesterone when administered in combination but not alone cause the development of numerous endbuds in the mouse mammary gland. KGF in estrogen- and progesterone- pretreated mice causes the growth of dilated ducts, hyperplastic epithelium within ducts and endbuds, and a fibrous metamorphosis of periductal adipose tissue. The mammary epithelial hyperplasia caused by KGF is rapidly reversible in both mice and rats after cessation of KGF treatment. The spectrum of KGF-, estrogen-, and progesterone-induced mammary histopathology in mice provides a model for the study of fibrocystic and hyperplastic breast disease.

Original languageEnglish (US)
Pages (from-to)1015-1022
Number of pages8
JournalAmerican Journal of Pathology
Volume145
Issue number5
StatePublished - Nov 1 1994

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yi, E. S., Bedoya, A. A., Lee, H., Kim, S., Housley, R. M., Aukerman, S. L., Tarpley, J. E., Starnes, C., Yin, S., Pierce, G. F., & Ulich, T. R. (1994). Keratinocyte growth factor causes cystic dilation of the mammary glands of mice: Interactions of keratinocyte growth factor, estrogen, and progesterone in vivo. American Journal of Pathology, 145(5), 1015-1022.