Expression of Intestinal Trefoil Factor (TFF-3) in Hepatocellular Carcinoma

Khoury, Thaer; Chadha, Krishdeep; Javle, Milind; Donohue, Kathleen; LeVea, Charles; Iyer, Renuka; Okada, Haruhiko; Nagase, Hiroki; Tan, Dongfeng

doi:10.1385/ijgc:35:3:171

Cited by 25 publications

(19 citation statements)

References 20 publications

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“…Our result demonstrated that tumor cells of HCC highly expressed many angiogenic factors, which play a critical role in the angiogenesis of HCC. Several studies reported similar results of angiogenic factors including Ang-2, MT3-MMP [19], MMP-2, MMP-9 [20], Trefoil peptides-3 (TFF-3) [21], Thrombospondin-1 [22], Basic fibroblast growth factor (bFGF) [23]. VEGF plays a critical role in mediating angiogenesis in HCC [1,7].…”

Section: Discussionmentioning

confidence: 84%

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

et al. 2008

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The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 +/- 43.8/mm2 and 30.4 +/- 14.8/mm2, respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV.

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Section: Discussionmentioning

confidence: 84%

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

et al. 2008

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“…It is overexpressed in a wide range of human tumors of skin, breast, urogenital, gastrointestinal tract and liver (16)(17)(18)(19)(20)(21)(22)(23) and is thought to induce cancer cell growth. Tff3 overexpression appears to be a frequent event not only in spontaneous (23), transgenicinduced (23), chemically-induced (24) mouse liver tumors, but also in various risk factor-induced human HCC (23).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile of DNA binding protein A transgenic mice

Tobita

Kajino²,

Inami³

et al. 2006

Int J Oncol

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Abstract.We recently reported that the expression of dbpA (DNA binding protein A) is associated with advanced stages of human hepatocellular carcinoma (HCC) and that its transcription is positively regulated by E2F1, which is also implicated in hepatocarcinogenesis. To study the in vivo effect of dbpA on hepatocarcinogenesis, we generated the dbpA-transgenic mouse that specifically expressed a transgene in hepatocytes. Here, we studied the effect of dbpA on the expression of other cellular genes by using microarray analyses. The expression profiles from livers of 31-and 32-week-old male transgenic mice [Tg(+)] that did not show any morphological changes and from livers of their male wild-type littermates [Tg(-)] were compared. Expression differences detected by microarray analyses were validated by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA samples from livers of 3 pairs of Tg(+) and (-) mice. The 11 up-regulated genes included 7 carcinogenesis-related genes (Igfbp1, Tff3, Hpx, Orm2, Ctsl, Plg, Jdp1), and the 9 down-regulated genes included Car3 that is associated with the protection of cells from attack by oxygen radicals. We confirmed that the expression of Igfbp1 (insulin like growth factor binding protein 1) was reduced by siRNA targeting dbpA in the human HCC cell line. In conclusion, our present data suggested that dbpA could be positively involved in carcinogenesis by changing the expression profiles of cellular genes.

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“…gastric cancer [18], pancreatic cancer [19], hepatocellular carcinomas [20], colon carcinoma [21] and breast cancer [13,22]. Besides, TFF3 expression correlates with the tumor grade in hepatocellular carcinoma [23] and TFF3 is highly expressed in intestinal metaplasia and a marker for poor prognosis in gastric carcinoma [24]. On the other hand, TFF1-knockout mice develop gastric carcinomas and adenomas [25] and patients with gastric cancer usually display reduced TFF1 levels.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Philippeit¹,

Busch²,

Dünker³

2014

Cell Physiol Biochem

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Background: Recent studies demonstrated that epigenetic mechanisms are involved in the regulation of trefoil factor family (TFF) peptide expression in cancer. In human tissues with endogenous TFF1, TFF2 or TFF3 gene expression, the corresponding promoter is unmethylated and in organs without TFF expression, the promoter of the three genes is highly methylated. Methods: Retinoblastoma (Rb) cell lines were treated with the DNA methyltransferase inhibitor 5-Aza-2`deoxycytidine (5-Aza-dC), the histone deacetylase inhibitor 4-Phenylbutyric acid (PBA) or both and analyzed for changes (i) in TFF mRNA expression by Real-time PCR and (ii) in the methylation status of the TFF promoters by genomic bisulfite sequencing. Results: The degree of promoter methylation correlates with endogenous TFF expression in the retinoblastoma cell lines analyzed. Nearly all Rb cell lines exhibiting high endogenous TFF1 expression displayed low methylation of the CpGs in the corresponding promoter region. Low expression of TFF3 in Rb cell lines is linked with high density methylation of the TFF3 promoter. 5-Aza-dC treatment induced TFF1 and TFF3 expression in nearly all cell lines investigated and combined treatment with PBA further increased this effect. The number of methylated CpG dinucleotides of the TFF promoter is clearly reduced upon treatment with 5-Aza-dC and combined treatment with PBA further extended the degree of demethylation. Conclusion: Our data clearly show that the expression of TFF3 in retinoblastoma cell lines is epigenetically regulated, whereas the level of TFF1 and TFF2 seems to be regulated by other or additional mechanisms.

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Expression of Intestinal Trefoil Factor (TFF-3) in Hepatocellular Carcinoma

Abstract: TFF-3 is commonly expressed in HCC and its expression correlates with tumor grade.

Cited by 25 publications

References 20 publications

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

The angiogenic and prognostic implications of VEGF, Ang-1, Ang-2, and MMP-9 for hepatocellular carcinoma with background of hepatitis B virus

Gene expression profile of DNA binding protein A transgenic mice

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

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