Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients

Journé, Fabrice; Durbecq, Virginie; Chaboteaux, Carole; Rouas, Ghizlane; Laurent, Guy; Nonclercq, Denis; Sotiriou, Christos; Body, Jean‐Jacques; Larsimont, Denis

doi:10.1007/s10549-008-0094-2

Cited by 54 publications

(64 citation statements)

References 45 publications

(60 reference statements)

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“…This is supported by previous studies showing that FXR expression is down-regulated in hepatitis C virus-induced liver fibrosis and human HCC specimen (31,32) as well as studies in colon (33) and breast (34) cancer. Our gene profiling analysis further revealed that FXR Ϫ/Ϫ mice had similar gene expression alterations as human HCC, indicating a potential role of FXR in human HCC development.…”

Section: Discussionsupporting

confidence: 85%

Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression

Liu¹,

Meng

Lou

et al. 2012

Molecular Endocrinology

109

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Farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4) is a member of nuclear hormone receptor superfamily, which plays essential roles in metabolism of bile acids, lipid, and glucose. We previously showed spontaneously hepatocarcinogenesis in aged FXR(-/-) mice, but its relevance to human hepatocellular carcinoma (HCC) is unclear. Here, we report a systematical analysis of hepatocarcinogenesis in FXR(-/-) mice and FXR expression in human liver cancer. In this study, liver tissues obtained from FXR(-/-) and wild-type mice at different ages were compared by microarray gene profiling, histological staining, chemical analysis, and quantitative real-time PCR. Primary hepatic stellate cells and primary hepatocytes isolated from FXR(-/-) and wild-type mice were also analyzed and compared. The results showed that the altered genes in FXR(-/-) livers were mainly related to metabolism, inflammation, and fibrosis, which suggest that hepatocarcinogenesis in FXR(-/-) mice recapitulated the progression of human liver cancer. Indeed, FXR expression in human HCC was down-regulated compared with normal liver tissues. Furthermore, the proinflammatory cytokines, which were up-regulated in human HCC microenvironment, decreased FXR expression by inhibiting the transactivity of hepatic nuclear factor 1α on FXR gene promoter. Our study thereby demonstrates that the down-regulation of FXR has an important role in human hepatocarcinogenesis and FXR(-/-) mice provide a unique animal model for HCC study.

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Section: Discussionsupporting

confidence: 85%

Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression

Liu¹,

Meng

Lou

et al. 2012

Molecular Endocrinology

109

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“…They also act as signaling molecules and metabolic regulators through the farnesoid X receptor (FXR) [35]. The FXR is expressed in breast ductal epithelial cells, human breast cancer cell lines [36] and normal breast tissue [37]. Therefore, while the changes observed here most likely reflect liver metabolism, systemic changes in the bile acid profile could also have an effect on breast tissue.…”

Section: Discussionmentioning

confidence: 99%

Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention

Miller

Pappan

Thompson

et al. 2015

Cancer Prevention Research

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Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anti-cancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biological activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/post-intervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography (UPLC) coupled to a linear trap quadrupole (LTQ) system and gas chromatography mass spectrometry (GC-MS). Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database (HMDB) and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P’s<0.01), and significant increases in bile acids (P’s≤0.05) and multiple collagen breakdown products (P’s<0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell cycle regulatory protein, in patient tumor tissues (P’s≤0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Further, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting.

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“…Hydrophobic BAs, such as deoxycholic acid (DCA) or lithocholic acid (LCA), have been reported to induce cell death in some cultured intestinal epithelial cell lines (7)(8)(9). Chenodeoxycholic acid (CDCA) enhances proliferation of certain cell lines (10), but the direct effect of each BA on epithelial cells depends on the cell line used. Moreover, in vivo, a variety of BAs exist at the same time in various tissues and intestinal contents, making it difficult to determine the precise influence of BAs on proliferation or survival of epithelial cells.…”

mentioning

confidence: 99%

Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS

Hagio

Matsumoto

Fukushima

et al. 2009

Journal of Lipid Research

140

106

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To evaluate bile acid (BA) metabolism in detail, we established a method for analyzing BA composition in various tissues and intestinal contents using ultra performance liquid chromatography/electrospray ionization mass spectrometry (UPLC/ESI-MS). Twenty-two individual BAs were determined simultaneously from extracts. We applied this method to define the differences in BA metabolism between two rat strains, WKAH and DA. The amount of total bile acids (TBAs) in the liver was significantly higher in WKAH than in DA rats. In contrast, TBA concentration in jejunal content, cecal content, colorectal content, and feces was higher in DA rats than in WKAH rats. Nearly all BAs in the liver were in the taurine-or glycine-conjugated form in DA rats, and the proportion of conjugated liver BAs was up to 75% in WKAH rats. Similar trends were observed for the conjugation rates in bile. The most abundant secondary BA in cecal content, colorectal content, and feces was hyodeoxycholic acid in WKAH rats and v-muricholic acid in DA rats. Analyzing detailed BA profiles, including conjugation status, in a single run is possible using UPLC/ESI-MS. This method will be useful for investigating the roles of BA metabolism under physiological and pathological conditions.-Hagio, M., M. Matsumoto, M. Fukushima, H. Hara, and S. Ishizuka. Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS. J. Lipid Res. 2009. 50: 173-180. Supplementary key words HPLC • ultra performance liquid chromatography • electrospray ionization mass spectrometry

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Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients

Cited by 54 publications

References 45 publications

Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression

Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression

Plasma Metabolomic Profiles of Breast Cancer Patients after Short-term Limonene Intervention

Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS

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