J Korean Med Sci.  2006 Oct;21(5):891-896. 10.3346/jkms.2006.21.5.891.

Expression of the RERG Gene is Gender-Dependent in Hepatocellular Carcinoma and Regulated by Histone Deacetyltransferases

• Wang AG
• Fang W
• Han YH
• Cho SM
• Choi JY
• Lee KH
• Kim WH
• Kim JM
• Park MG
• Yu DY
• Kim NS
• Lee DS

• KMID: 1781911
• DOI: http://doi.org/10.3346/jkms.2006.21.5.891

Abstract

Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.

Keyword

Ras-Related Estrogen-Regulated and Growth-Inhibitory Gene (RERG); Carcinoma, Hepatocel-lular; Sex; Histone Acetyltransferases

MeSH Terms

Signal Transduction
Sex Factors
Mice, Transgenic
Mice, Inbred C57BL
Mice
Male
Liver Neoplasms/*genetics
Humans
Histone Deacetylases/*physiology
Hepatocytes/metabolism
Growth Inhibitors/*genetics
*Genes, ras
*Gene Expression Regulation, Neoplastic
Female
Estrogens/*pharmacology
Estrogen Receptor alpha/analysis
Cell Proliferation
Animals

Figure

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  Fig. 1 RERG expression in human hepatocellular carcinoma. RERG expression was analyzed by RT-PCR. GAPDH was used as a quantitative control. M, size marker; N, adjacent peri-tumoral tissues; T, tumoral tissues.

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  Fig. 2 Expression of the estrogen receptor variant ER-α in human HCC. ER-α expression was analyzed by RT-RCR. T, tumoral tissues; N, adjacent peri-tumoral tissues.

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  Fig. 3 RERG expression in liver tissues of and H-ras12V transgenic mice. RERG expression was analyzed by RT-PCR. Liver or tumor tissues from 9-month-old male (A) and 14-month-old female (B) H-ras12V transgenic mice were sampled.

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  Fig. 4 RERG expression in liver tissues of hepatectomized mice. RT-PCR analysis of RERG expression in liver tissues on days 0-4, and 5 after hepatectomy. Three independent hepatectomy experiments were performed. GAPDH was used as a quantitative control. M, size marker; Wt, normal control littermate; N, peri-tumoral liver tissues; T, liver tumor tissues; Tg, H-ras12V transgenic mice; N-H, non-hepatectomized mice.

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  Fig. 5 RERG expression in trichostatin A (TSA)-treated cells. Expression of the gene was analyzed by RT-PCR. NIH3T3, MDA-MD0-231, and Hepa1-6 cells were treated with 0.5 µM or 1 µm of the histone deacetyltransferases (HDAC) inhibitor TSA. GAPDH was used as a quantitative control. M, size marker.

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