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Open Access Research article

Hepatocyte RXRalpha deficiency in matured and aged mice: impact on the expression of cancer-related hepatic genes in a gender-specific manner

Minglei Guo1, Lei Gong2, Lin He1, Lois Lehman-McKeeman2 and Yu-Jui Yvonne Wan1*

Author Affiliations

1 Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66103, USA

2 Discovery Toxicology, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA

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BMC Genomics 2008, 9:403  doi:10.1186/1471-2164-9-403

Published: 28 August 2008

Abstract

Background

The occurrence of liver cancer is higher in males than in females, and the incidence increases during aging. Signaling pathways regulated by retinoid × receptor α (RXRα) are involved in hepatocellular carcinogenesis. The phenotype of hepatocyte RXRα deficient mice is different between genders. To explore the impact of hepatocyte RXRα deficiency on gender-dependent hepatic gene expression, we compared the expression profiles of cancer-related genes in 6 and 24 month old male and female mice.

Results

In 6 month old mice, male mutant mice showed more cancer-related genes with alteration in mRNA levels than females did (195 vs. 60). In aged mice (24 month), female mutant mice showed greater deviation in mRNA expression levels of cancer-related genes than their male counterparts (149 vs. 82). The genes were classified into five categories according to their role in carcinogenesis: apoptosis, metastasis, cell growth, stress, and immune respnse. In each category, dependent upon age and gender, the genes as well as the number of genes with altered mRNA levels due to RXRα deficiency varies.

Conclusion

The change in hepatic cancer-related gene expression profiles due to RXRα deficiency was gender- and age-dependent. The alteration of mRNA levels of cancer-related genes implied that aberrant RXRα signaling could potentially increase the risk of liver cancer and that retinoid signaling might contribute to gender- and age-associated liver cancer incidence.