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

Abstract

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-1beta (HNF-1beta) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1alpha. In contrast to HNF-1alpha, HNF-1beta is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1beta plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1beta expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1beta germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1beta 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-1beta is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1beta is down-regulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1beta expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1beta status in human urogenital neoplasms and discuss its role in tumorigenesis.