vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.

Rey-Campos, Javier; Chouard, Tanguy; Yaniv, Moshe; Cereghini, Silvia

doi:10.1002/j.1460-2075.1991.tb07665.x

Cited by 266 publications

(231 citation statements)

References 44 publications

(60 reference statements)

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“…HNF-1beta is a transcription activator that regulates the promoters or enhancers of genes that are expressed in a liver-specific manner, such as albumin and alpha-fetoprotein. [16][17][18] In normal tissue, HNF-1beta is expressed not only in the liver, but also in the digestive tract, pancreas, and kidney, where it plays a role as a major regulator of glucose homeostasis. 19 It has been shown that the reduction of HNF-1beta expression by RNA interference induced apoptosis in ovarian clear cell carcinoma cell lines, suggesting that HNF-1beta expression is essential for the survival of clear cell carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

2006

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Clear cell tumors of the ovary are frequently associated with ovarian endometriosis. Clinicopathologically, it has been suggested that clear cell tumors develop from endometriosis, but there has been little molecular evidence supporting this speculation. Microarray analysis revealed recently that hepatocyte nuclear factor1beta (HNF-1beta) was significantly upregulated in clear cell carcinoma of the ovary. In the present study, we examined 30 clear cell tumors (26 malignant, three borderline, and one benign) and 40 endometriotic cysts to clarify if differentiation into the clear cell lineage already begins in ovarian endometriosis. All of the 30 clear cell tumors, including borderline and benign ones, showed immunohistochemical expression of HNF-1beta in the nucleus, while other types of ovarian epithelial tumors (endometrioid, serous, mucinous, and Brenner tumors) rarely expressed it. Among 30 clear cell tumors, 17 (56%) cases were associated with endometriosis, and endometriotic epithelium was identified in 12 cases. In nine of the 12 cases, distinct nuclear immunostaining for HNF-1beta was detected in the endometriotic epithelium, as well as in the clear cell tumor. HNF-1beta expression was observed either in atypical endometriosis (four cases), or in endometriosis of a reactive nature (five cases). Furthermore, 16 of 40 (40%) endometriotic cysts without a neoplasm also expressed HNF-1beta, and the expression was almost exclusively observed in the epithelium showing inflammatory atypia. Our results indicate that HNF-1beta is an excellent molecular marker for ovarian clear cell tumors, including benign, borderline and malignant lesions. Early differentiation into the clear cell lineage takes place in ovarian endometriosis, not only in atypical endometriosis, but also in endometriosis with degenerative and regenerative changes, and this is probably responsible for the frequent occurrence of clear cell carcinoma in ovarian endometriosis. Keywords: ovary; clear cell tumor; endometriosis; hepatocyte nuclear factor-1beta; histogenesis Among malignant epithelial tumors of the ovary, clear cell carcinomas, as well as endometrioid adenocarcinomas, are most frequently associated with ovarian endometriosis. The frequency of endometriosis is reportedly between 21 and 54% in large series of clear cell carcinomas. [1][2][3][4][5] In addition, an atypical glandular change in endometriosis, the socalled atypical endometriosis, is often present associated with clear cell carcinomas, while it is rare in endometriosis without a neoplasm. 2,6,7 Thus, many clinicopathological studies have strongly suggested a malignant transformation of endometriosis to clear cell carcinomas, but little molecular evidence exists to support the notion that endometriosis is the precursor of clear cell carcinomas. A molecular genetic study showed that ovarian endometriosis and its adjacent carcinoma shared a common allelotype; however, few clear cell carcinomas were subjected to this study. 8 Recently, a study using an oligonucleotide array technique...

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Section: Discussionmentioning

confidence: 99%

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

2006

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“…HNF1 and HNF1, two members of the HNF1 transcription factor family, share amino-terminal dimerization domain and POU-like DNA-binding homeo domain, but not carboxyl-terminal transcriptional activation domain, and they bind DNA as homodimers or heterodimers [24,34,35]. Our data demonstrated that in the human Cbg proximal promoter, HNF1 or HNF1 had different effect on the basal promoter activity.…”

Section: Discussionmentioning

confidence: 69%

Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity

Lei

et al. 2012

Sci. China Life Sci.

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Corticosteroid-binding globulin (CBG) is a high-affinity plasma protein that transports glucocorticoids and progesterone. Others and we have reported non-synonymous single nucleotide polymorphisms (SNPs) that influence CBG production or steroid-binding activity. However, no promoter polymorphisms affecting the transcription of human CBG gene (Cbg) have been reported. In the present study we investigated function implications of six promoter SNPs, including 26 C/G, 54 C/T, 144 G/C, 161 A/G, 205 C/A, and 443/444 AG/, five of which are located within the first 205 base pairs of 5′-flanking region and close to the highly conserved footprinted elements, TATA-box, or CCAAT-box. Luciferase reporter assays demonstrated that basal activity of the promoter carrying 54 T or 161 G was significantly enhanced. The first three polymorphisms, 26 C/G, 54 C/T, and 144 G/C located close to the putative hepatic nuclear factor (HNF) 1 binding elements, altered the transactivation effect of HNF1. We also found a negative promoter response to dexamethasone-activated glucocorticoid receptor (GR) , although none of the SNPs affected its transrepression function. Our results suggest that human Cbg 26 C/G, 54 C/T, 144 G/C, and 161 A/G promoter polymorphisms alter transcriptional activity, and further studies are awaited to explore their association with physiological and pathological conditions. , both of which are well-known hormones for pregnancy maintenance or labor onset. While CBG mainly binds >80% of cortisol in human peripheral blood [3], at the maternal-fetal interface CBG will be occupied by the very high concentrations of progesterone, which is several fold higher than those of cortisol [6]. In the circulation of women during mid-late pregnancy, approximately 10% of CBG steroid-binding sites are occupied by progesterone, versus <1% in non-pregnant women [5]. Plasma CBG levels rise progressively through gestation until term pregnancy [7], and so do blood cortisol and progesterone levels. Maternal plasma CBG, total and free cortisol concentrations are reduced in pre-eclampsia and gestational hypertension patients, and this may be a consequence of decreased Cbg synthesis driven by cytokines or increased degradation driven by inflammation [7]. SPECIAL TOPIC

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“…TCF1 and TCF2, respectively, encode the transcription factors hepatocyte nuclear factor 1a and b (HNF1a and HNF1b), two POU-homeodomain proteins that bind to an essential element in the proximal promoter sequences of albumin and many other tissue-specific genes and are associated with development, metabolism and cancer (Cereghini et al, 1987;Courtois et al, 1987;Frain et al, 1989;Rey-Campos et al, 1991). For instance, TCF2 defects cause developmental abnormalities in multiple tissues, including kidney and pancreas (Horikawa et al, 1997;Haumaitre et al, 2005), and Bluteau et al (2002) identified biallelic mutations of TCF1 in hepatic adenomas (Bluteau et al, 2002).…”

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confidence: 99%

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines

et al. 2006

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Transcription factor 2 gene (TCF2) encodes hepatocyte nuclear factor 1b (HNF1b), a transcription factor associated with development and metabolism. Mutation of TCF2 has been observed in renal cell cancer, and by screening aberrantly methylated genes, we have now identified TCF2 as a target for epigenetic inactivation in ovarian cancer. TCF2 was methylated in 53% of ovarian cancer cell lines and 26% of primary ovarian cancers, resulting in loss of the gene's expression. TCF2 expression was restored by treating cells with a methyltransferase inhibitor, 5-aza-2 0 deoxycitidine (5-aza-dC). In addition, chromatin immunoprecipitation showed deacetylation of histone H3 in methylated cells and, when combined with 5-aza-dC, the histone deacetylase inhibitor trichostatin A synergistically induced TCF2 expression. Epigenetic inactivation of TCF2 was also seen in colorectal, gastric and pancreatic cell lines, suggesting general involvement of epigenetic inactivation of TCF2 in tumorigenesis. Restoration of TCF2 expression induced expression of HNF4a, a transcriptional target of HNF1b, indicating that epigenetic silencing of TCF2 leads to alteration of the hepatocyte nuclear factor network in tumours. These results suggest that TCF2 is involved in the development of ovarian cancers and may represent a useful target for their detection and treatment.

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vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.

Cited by 266 publications

References 44 publications

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines

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