Hepatocyte Nuclear Factor 3 (Winged Helix Domain) Activates Trefoil Factor Gene TFF1 through a Binding Motif Adjacent to the TATAA Box

Beck, Stefanie; Sommer, Patricia; Silva, Elisabeth Dos Santos; Blin, Nikolaus; Gött, Peter

doi:10.1089/104454999315547

Cited by 59 publications

(40 citation statements)

References 31 publications

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“…Additionally, it includes in its sequence two HpaII restriction sites (CCGG) (positions Ϫ85 and Ϫ21) previously shown by Fujimoto et al (2000) to be targets in TFF1 promoter methylation. Further, CpG site Ϫ20 is four nucleotides downstream of the TATA box; CpG site Ϫ56 is seven nucleotides upstream of motif 4, the binding site of hepatocyte nuclear factor 3␤, previously shown to activate TFF1 expression (Beck et al, 1999), and three nucleotides downstream of the GATA-6 binding site, known to be TFF1-activating (Al azzeh et al, 2000). As expected from the TFF1-expressing nature of the gastric carcinoma-derived cell line GP220, a predominantly negative promoter methylation pattern was established.…”

Section: Discussionmentioning

confidence: 99%

Loss of Heterozygosity and Promoter Methylation, but not Mutation, May Underlie Loss of TFF1 in Gastric Carcinoma

Carvalho

Kayademir

Soares

et al. 2002

Laboratory Investigation

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SUMMARY:It has been advanced that the trefoil factor (TFF) 1 gene is a candidate tumor-suppressor gene and may be involved in the development and/or progression of human gastric cancer. We aimed to clarify the putative role of TFF1 in gastric carcinogenesis. Ninety gastric carcinomas and eight gastric carcinoma-derived cell lines were screened for TFF1 mutations; subsets of the primary tumors and of the cell lines were subjected to loss of heterozygosity (LOH), immunohistochemistry, and promoter methylation analyses. TFF1 mutations were not detected in any of 90 gastric carcinomas. Eight (28%) of 28 informative cases displayed LOH at the TFF1 locus and absence of TFF1 staining by immunohistochemistry. These results indicate a frequent loss of TFF1 expression in gastric carcinomas through a mutation-independent mechanism. Extensive TFF1 promoter methylation was observed in nonexpressing gastric carcinoma-derived cell lines and tissues. Expressing cell lines, as well as normal gastric mucosa, presented little or no methylation of the promoter. Gastric carcinoma DNA presented de novo methylation of the promoter. These results point to the involvement of promoter methylation in the shutting down of TFF1. We conclude that TFF1 point mutations seem to be a rare event in gastric carcinogenesis. The loss of expression of TFF1 in a proportion of gastric carcinomas may be explained by LOH and methylation of the TFF1 promoter region. Our results further support the role of TFF1 inactivation in gastric carcinogenesis, in agreement with the results obtained in the Tff1-knockout mice model. (Lab Invest 2002, 82:1319 -1326.

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Section: Discussionmentioning

confidence: 99%

Loss of Heterozygosity and Promoter Methylation, but not Mutation, May Underlie Loss of TFF1 in Gastric Carcinoma

Carvalho

Kayademir

Soares

et al. 2002

Laboratory Investigation

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“…As a stimulator, it functions as a pioneer factor that binds to chromatinised DNA, opens the chromatin and enhances binding of oestrogen receptor-alpha (ERα) to its target genes such as TFF1 (trefoil factor 1; pS2) (Beck et al, 1999). In addition to modulating ER activity, FOXA1 also directly binds to the ESR1 (oestrogen receptor 1) promoter and is required for expression of ER mRNA and protein in breast cancer cells (Bernardo et al, 2010).…”

Section: Roles Of Foxa1 In Breast Cancermentioning

confidence: 99%

FOXA1: a Promising Prognostic Marker in Breast Cancer

Luo²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Accurate diagnosis and proper monitoring of cancer patients remain important obstacles for successful cancer treatment. The search for cancer biomarkers can aid in more accurate prediction of clinical outcome and may also reveal novel predictive factors and therapeutic targets. One such prognostic marker seems to be FOXA1. Many studies have shown that FOXA1 is strongly expressed in a vast majority of cancers, including breast cancer, in which high expression is associated with a good prognosis. In this review, we summarize the role of this transcription factor in the development and prognosis of breast cancer in the hope of providing insights into utility of FOXA1 as a novel biomarker.

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“…22 Furthermore, estradiol induction of TFF1 is reportedly inhibited by tamoxifen. 22 Another gene that co-clusters with ESR1, hepatocyte nuclear factor 3, alpha (HNF3A) activates TFF1 23 (Table 1). HNF3A was shown previously to co-cluster with ESR1 in expression profiles from 65 breast tumors by Perou et al 24 Three additional genes listed in Table 1 also co-clustered with ESR1 in the report by Perou et al: LIV-1; hepsin (HPN) a transmembrane protease which plays an essential role in cell growth and maintenance of cell morphology; 25 X-box binding protein 1 (XBP1) which binds to the HLA-DR-alpha promoter and may act as a transcription factor in B-cells.…”

Section: Wwwnaturecom/tpjmentioning

confidence: 99%

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

et al. 2001

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The estrogen receptor plays a critical role in the pathogenesis and clinical behavior of breast cancer. To better understand the molecular basis of estrogen-dependent forms of this disease we studied gene expression profiles from 53 primary breast cancer biopsies. Gene expression data for more than 7000 genes were generated from each tumor sample with oligo microarrays. A standard correlation-clustering algorithm identified 18 genes that co-clustered with estrogen receptor alpha. Eleven of these genes had previously been associated with estrogen regulation or breast tumorigenesis including trefoil factor 1 and estrogen regulated LIV-1. Additional study of these 18 genes may further delineate the role of estrogen receptor in breast cancer, generate new predictive biomarkers for response to endocrine therapies and identify novel therapeutic targets. The Pharmacogenomics Journal ( BACKGROUNDThe estrogen receptor is a ligand-activated transcription factor containing hormone binding, DNA binding and transcription activation domains. 1 It is expressed in normal breast and 50-80% of breast cancers, depending on the assay used. 2-4 Estrogen receptor (ER) is a favorable prognostic factor and ER positive malignancies have a lower risk of relapse and a better overall survival. 5 However, ESR1 analysis is most useful in predicting response to endocrine therapies, although approximately half of all ER-positive cancers do not respond to antiestrogens or estrogen deprivation therapies. 6 The molecular basis for ESR1-positive, endocrine therapy-resistant disease is not well understood. Somatic mutations in ESR1 are rare, even in breast cancers that have acquired resistances to endocrine therapies. This finding has focused attention on other mechanisms, including the overexpression of tyrosone-kinase linked growth factor receptors, transcriptional coactivators such as AIB1 (amplified in breast cancer 1) or cell cycle regulators including Cyclin D1. Additional possibilities include mutations in other genes involved in the regulation of estrogen-dependent growth.Expression of the estrogen-regulated genes, progesterone receptor (PGR) and trefoil factor 1 (TFF1 or PS2) indicate the presence of a functional and activated ER. 7 Both of these proteins are predictive biomarkers for breast cancer endocrine therapy, although less valuable than ER in distinguishing estrogen-dependent from estrogen-independent breast cancer. The use of PGR improves upon the predictive value of ER alone, yet ෂ 40% of tumors that express both ER and PGR fail to respond to endocrine treatments in the metastatic setting. 8 Similarly, TFF1 is associated with a good prognosis and predicts a positive response to hormonal therapy, but it has not proved to be sufficient as a predictive biomarker for routine evaluation of breast cancer. 9 Thus, PGR and TFF1 may be modestly useful

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Hepatocyte Nuclear Factor 3 (Winged Helix Domain) Activates Trefoil Factor Gene TFF1 through a Binding Motif Adjacent to the TATAA Box

Cited by 59 publications

References 31 publications

Loss of Heterozygosity and Promoter Methylation, but not Mutation, May Underlie Loss of TFF1 in Gastric Carcinoma

Loss of Heterozygosity and Promoter Methylation, but not Mutation, May Underlie Loss of TFF1 in Gastric Carcinoma

FOXA1: a Promising Prognostic Marker in Breast Cancer

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

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