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Tumor-suppressor effect of interferon regulatory factor-1 in human hepatocellular carcinoma
Y Moriyama1, S Nishiguchi, A Tamori
1Second Department of Biochemistry, Osaka City University Medical School, Osaka 545-8585, Japan.
Abstract:
IFN regulatory factor-1 (IRF-1) regulates the IFN system, inhibits cell growth, and has tumor-suppressor activities. p21 is a universal cyclin-dependent kinase inhibitor, the induction of which depends on both p53 and IRF-1 in mouse embryonic fibroblasts. The expression of p21 in hepatocellular carcinomas (HCCs) is regulated by wild-type p53. We examined the expressions of IRF-1 and p21 in 32 HCCs by quantitative reverse transcription-PCR and the mutation p53 gene in 32 HCCs by single-strand conformation polymorphism and direct sequencing. The expression of IRF-1 mRNA in 15 of 32 HCCs was lower than that in adjacent noncancerous tissue. IRF-1 mRNA expression was reduced in 0 of 3 specimens of well-differentiated HCC, 9 of 21 (42%) specimens of moderately differentiated HCC, and 6 of 8 (75%) specimens of poorly differentiated HCC. IRF-1 mRNA expression was significantly lower in tumors with portal thrombus than in those without portal thrombus (P = 0.003). p53 mutations were detected in 7 of 32 HCCS: p21 expression was reduced in 6 of the 7 (86%) HCCs with p53 mutations. In contrast, p21 expression was reduced in 13 of 25 (52%) HCCs with wild-type p53. IRF-1 expression was reduced in 7 of 13 (53%) HCCs with both wild-type p53 and reduced expression of p21. These results suggest that IRF-1 may be a tumor-suppressor gene for HCC and that IRF-1 is related to p21 expression in HCC with wild-type p53.
Insights
Interferon regulatory factor-1 (IRF-1) may act as a tumor suppressor in hepatocellular carcinoma (HCC). Reduced IRF-1 expression correlates with advanced HCC and is linked to p21 expression in wild-type p53 HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Interferon regulatory factor-1 (IRF-1) is known to regulate the interferon system, inhibit cell growth, and possess tumor-suppressor activities.
- p21 is a critical cyclin-dependent kinase inhibitor, with its induction dependent on both p53 and IRF-1.
- p21 expression in hepatocellular carcinomas (HCCs) is influenced by wild-type p53.
Purpose of the Study:
- To investigate the expression levels of IRF-1 and p21 in HCC tissues.
- To analyze the correlation between IRF-1 and p21 expression and clinicopathological features of HCC, including p53 gene mutations.
Main Methods:
- Quantitative reverse transcription-PCR was used to assess IRF-1 and p21 mRNA expression in 32 HCC samples and adjacent noncancerous tissues.
- Single-strand conformation polymorphism and direct sequencing were employed to detect p53 gene mutations in the HCC samples.
Main Results:
- Reduced IRF-1 mRNA expression was observed in 15 out of 32 HCCs compared to adjacent noncancerous tissue, with higher rates in poorly differentiated HCC and tumors with portal thrombus.
- p53 mutations were found in 7 HCCs, and reduced p21 expression was noted in 86% of these cases.
- Reduced IRF-1 expression was found in 53% of HCCs with wild-type p53 and reduced p21 expression, suggesting a relationship between IRF-1 and p21 in this subset.
Conclusions:
- IRF-1 may function as a tumor suppressor gene in the development of HCC.
- IRF-1 expression is associated with p21 expression in HCC cases with wild-type p53, indicating a potential regulatory pathway.