The Expression of Cancer-Related Genes in Aging Mouse Liver is RXRα and Gender Dependent

Previous reports have demonstrated that gene expression profiles are modified in several tissue types including liver during the aging process and that such alterations might impact on the development and advancement of certain diseases. To understand the affect of aging on liver cancer, we have studied the expression pattern of cancer-related genes in aging mouse livers. Retinoid x receptor α (RXRα) is a transcription factor that is highly expressed in the liver. RXRα-regulated pathways are implicated in liver detoxification and carcinogenesis. In addition, liver cancer incidence is higher in males than in females. Thus, we have also studied the effects of hepatic RXRα and gender on regulating those cancer-related genes in aging mouse livers.

Hepatic cancer-related gene expression patterns were compared between old (24-month-old) and young mature (6-month-old) wild type as well as hepatocyte RXRα-deficient C57BL/6J mice in both genders. cDNA microarray was performed and quantitative reverse transcription-polymerase chain reaction assays were employed to validate part of our results. In aged male mouse liver, genes associated with apoptosis, metastasis, cell cycle transition, and DNA repair showed changes in expression levels. In female aged mouse liver, the most notable variations were found in genes that are related to the immune system. In addition, the expression pattern is RXRα dependent.

Our results suggested that specific sets of genes, which are regulated by gender and RXRα, might contribute to the increase in liver cancer incidence observed with age.