Hepatocyte nuclear factor-1ß(HNF-1ß) in human urogenital organs: Its expression and role in embryogenesis and tumorigenesis

Noriko Kato and Teiichi Motoyama

Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.

Offprint requests to: Noriko Kato, Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585 Japan. e-mail: nkato@med.id.yamagata-u.ac.jp


Summary. Molecules responsible for embryogenesis are often involved in tumorigenesis. Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge of such molecules. Hepatocyte nuclear factor-1ß (HNF-1ß) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1α. In contrast to HNF-1α, HNF-1ß is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1ß plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1ß expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1ß germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1ß is aberrantly up-regulated in clear cell carcinoma of the ovary, which is a carcinoma of müllerian nature, but which was initially misnamed “mesonephroma”. HNF-1ß is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1ß is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1ß expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1ß status in human urogenital neoplasms and discuss its role in tumorigenesis. Histol Histopathol 24, 1479-1486 (2009)

Key words: Hepatocyte nuclear factor-1ß, Urogenital organs, Human, Embryogenesis, Clear cell carcinoma of ovary

DOI: 10.14670/HH-24.1479