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

Kato N, Noriko Kato, Motoyama T, Teiichi Motoyama
Histology and histopathology · 2009 · vol. 24(11) , pp. 1479–86 · doi:10.14670/HH-24.1479 · PMID:19760597
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This review details hepatocyte nuclear factor-1beta (HNF-1beta) expression during human urogenital development and its altered roles in urogenital tumors like ovarian clear cell carcinoma and renal neoplasms.

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This review examines the expression and function of hepatocyte nuclear factor-1beta (HNF-1beta) during human urogenital embryogenesis and its aberrant regulation in various neoplasms. The authors detail how HNF-1beta is essential for the development of mesonephric duct derivatives and the metanephros, with germline mutations leading to structural malformations in these tissues. In tumorigenesis, the paper highlights that HNF-1beta is commonly up-regulated in ovarian clear cell carcinoma and is also expressed in ovarian endometriosis, suggesting a potential link between the two conditions. Conversely, the transcription factor is down-regulated in renal neoplasms such as chromophobe cell carcinoma. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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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.
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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: [email protected] 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

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endometriosis

MeSH descriptors

Hepatocyte Nuclear Factor 1-beta Urogenital Neoplasms Urogenital System Urogenital System Urogenital System Embryonic Development Embryonic Development Hepatocyte Nuclear Factor 1-beta Hepatocyte Nuclear Factor 1-beta Humans Humans Urogenital Neoplasms Urogenital Neoplasms Urogenital System Urogenital System

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