Induction of c-fos and c-myc oncogene expression in the pyloric mucosa of rat stomach by N-methyl-N′-nitro-N-nitrosoguanidine and taurocholate

Furihata, Chie; Yamakoshi, Akira; Hatta, Akiko; Tatematsu, Masae; Iwata, Hitoshi; Hayashi, Kenshi; Umezawa, Kazuo; Matsushima, Taijiro

doi:10.1016/0304-3835(94)90322-0

Cited by 10 publications

(6 citation statements)

References 9 publications

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“…Additionally, TCA increased Myc expression in primary hepatocytes from Fxr ‐null and Fxr ΔHep mice, indicating that not only Fxr disruption but also TCA increases are required for Myc activation in hepatocytes. TCA or TDCA have been reported to cause gastric or intestinal epithelial cell proliferation, respectively, through up‐regulating Myc , but to our knowledge, this is the first demonstration that TCA induces Myc expression in Fxr ‐null hepatocytes. Future studies are needed to clarify the molecular mechanisms on how TCA induces Myc expression only in Fxr ‐null hepatocytes.…”

Section: Discussionmentioning

confidence: 66%

Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development

et al. 2018

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Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, and an association between altered bile acid (BA) metabolism, down‐regulation of farnesoid X receptor (FXR), which is a master regulator of BA metabolism, and hepatocarcinogenesis has been documented. While global FXR deficiency in mice results in spontaneous HCC with aging, the contribution of tissue‐specific FXR deficiency to hepatocarcinogenesis remains unclear. In this study, the prevalence of hepatic tumors, expression of genes related to tumorigenesis, and serum/liver BA levels were compared among male whole‐body Fxr‐null, hepatocyte‐specific Fxr‐null (Fxr ∆Hep), and enterocyte‐specific Fxr‐null (Fxr ∆IE) mice at the age of 3, 14, and 20 months. More than 90% of 20‐month‐old whole‐body Fxr‐null mice had hepatic tumors with enhanced hepatic expression of myelocytomatosis oncogene (Myc) and cyclin‐dependent kinase 4 (Cdk4) messenger RNAs (mRNAs) and elevated serum taurocholate (TCA) and tauromuricholate (TMCA) and their respective unconjugated derivatives. The incidence of hepatic tumors was significantly lower in Fxr ∆Hep and Fxr ∆IE mice (20% and 5%, respectively), and the increases in Myc and Cdk4 mRNA or serum BA concentrations were not detected in these mice compared to Fxr floxed [fl]/fl mice; a similar tendency was observed in 14‐month‐old mice. However, increased hepatic c‐Myc protein expression was found only in Fxr‐null mice at the age of 3, 14, and 20 months. Treatment with TCA induced Myc expression in Fxr‐null cultured primary mouse hepatocytes but not in wild‐type (WT) mouse hepatocytes, demonstrating that the combination of hepatocyte FXR disruption with elevated TCA is required for Myc induction and ensuing age‐dependent hepatocarcinogenesis in Fxr‐null mice. Conclusion: There is a relatively low risk of hepatic tumors by inhibition of FXR in enterocytes, likely due to the lack of increased TCA and Myc induction.

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Section: Discussionmentioning

confidence: 66%

Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development

et al. 2018

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“…Their experiment suggested that six bile acids, but not taurolithocholic acid sodium salt, had potential tumor-promoting activities in the pyloric mucosa of the rat stomach. Furihata et al [54] also reported that sodium taurocholate and MNNG induced a transient increase in c-fos and c-myc expression in the pyloric gland of F344 rats [54]. These results demonstrated the carcinogenic promoting activity of bile acids, although none of these experiments proved that bile acid itself is an initiator.…”

Section: Mucosal Injury and Cell Proliferation Induced By Bile Juicementioning

confidence: 73%

Duodenogastric reflux and gastric stump carcinoma

Kondo

2002

Gastric Cancer

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“…The genotoxic glandular stomach and forestomach carcinogen MNNG does cause overexpression of c-fos and c-myc in the pyloric mucosa of rats 30 min to 3 hr after intragastric doses of 5, 15, and 50 mg/kg BW (8), but these doses are much lower than that usually applied (150 mg/kg BW) to induce toxicity. It is thus possible that catechol might induce protooncogene expression at lower dose levels without or with only low toxicity.…”

Section: Discussionmentioning

confidence: 94%

Sequential Morphological and Biological Changes in the Glandular Stomach Induced by Oral Administration of Catechol to Male F344 Rats

et al. 1999

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Histogenesis and mechanisms of catechol-induced rat glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 5 or 6 rats were treated with dietary catechol at doses of 1, 0.5, 0.1, and 0.01% for 12 hr or for 1, 2, 3, or 7 days or at a dose of 0.8% for 1, 2, 4, 12, and 24 wk; rats were then euthanatized. The initial morphological changes were edema of the gastric wall, inflammatory-cell infiltration, erosion in the pyloric region close to the duodenum, and considerable increase in apoptosis at 12 hr; later, changes included augmented DNA synthesis and cell proliferation, as evaluated by bromodeoxyuridine labeling index and thickness of mucosa, respectively, on day 1. Downward hyperplasia due to excess regeneration appeared at edges of ulceration at week 2. This lesion disappeared, and then submucosal hyperplasia appeared in the course of adenoma development. Only slight expression of c -myc or c-fos was apparent after 30-min oral administration or 1-, 3-, and 6-hr oral administration of catechol. No increase in lipid peroxide levels was evident in gastric epithelium fed catechol for 1 wk.

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Induction of c-fos and c-myc oncogene expression in the pyloric mucosa of rat stomach by N-methyl-N′-nitro-N-nitrosoguanidine and taurocholate

Cited by 10 publications

References 9 publications

Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development

Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development

Duodenogastric reflux and gastric stump carcinoma

Sequential Morphological and Biological Changes in the Glandular Stomach Induced by Oral Administration of Catechol to Male F344 Rats

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