Expression of retinoid X receptor α is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats

  • Authors:
    • Nobuhiro Ando
    • Masahito Shimizu
    • Masataka Okuno
    • Rie Matsushima-Nishiwaki
    • Hisashi Tsurumi
    • Takuji Tanaka
    • Hisataka Moriwaki
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/or.18.4.879
  • Pages: 879-884
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Abstract

The identification of the specific molecular targets, which underlie liver carcinogenesis is essential for the establishment of an effective strategy for the prevention and/or treatment of hepatocellular carcinomas (HCCs). We previously found that a malfunction of RXRα due to its aberrant phosphorylation was associated with the development of HCCs. However, it has remained unclear whether the abnormalities in the expression of RXRα or the other retinoid receptors play a role in the early stage of liver carcinogenesis. The present study was designed to determine whether alterations in the expression of RXRα and the other retinoid receptors RARα and RARβ are involved in hepatocarcinogenesis using a 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)-induced rat liver carcinogenesis model. We found that immunohistochemical expression of RXRα was decreased in liver cell tumors (HCCs and adenoma) and glutathione S-transferase placental form (GST-P)-positive foci, which is a precancerous lesion of HCC, when compared with the non-cancerous tissues. Western blot and RT-PCR analyses revealed a progressive decrease in the expression levels of RXRα, RARα, and RARβ proteins and their mRNAs in 3'-MeDAB-induced HCCs and their surrounding tissues, when compared with the normal liver tissues from the control group. Moreover, the expression level of β-catenin, the heterodimeric partner for both RXRα and RARα, was immunohistochemically observed in the cytoplasm and, in some cases, in the nucleus of HCC cells. The nuclear expression of cyclin D1, the downstream target molecule of β-catenin, was also increased in HCC cells when compared with their adjacent normal appearing tissues. Our findings suggest that loss of retinoid receptors, especially RXRα, plays a critical role in the chemically-induced rat liver carcinogenesis and this might be associated with the activation of β-catenin-related signaling pathway.

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October 2007
Volume 18 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ando N, Shimizu M, Okuno M, Matsushima-Nishiwaki R, Tsurumi H, Tanaka T and Moriwaki H: Expression of retinoid X receptor α is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats. Oncol Rep 18: 879-884, 2007
APA
Ando, N., Shimizu, M., Okuno, M., Matsushima-Nishiwaki, R., Tsurumi, H., Tanaka, T., & Moriwaki, H. (2007). Expression of retinoid X receptor α is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats. Oncology Reports, 18, 879-884. https://doi.org/10.3892/or.18.4.879
MLA
Ando, N., Shimizu, M., Okuno, M., Matsushima-Nishiwaki, R., Tsurumi, H., Tanaka, T., Moriwaki, H."Expression of retinoid X receptor α is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats". Oncology Reports 18.4 (2007): 879-884.
Chicago
Ando, N., Shimizu, M., Okuno, M., Matsushima-Nishiwaki, R., Tsurumi, H., Tanaka, T., Moriwaki, H."Expression of retinoid X receptor α is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats". Oncology Reports 18, no. 4 (2007): 879-884. https://doi.org/10.3892/or.18.4.879