The contribution of caveolin-1 genotype and phenotype to hepatocellular carcinoma

Chin Mu Hsu, Mei Due Yang, Chia Wen Tsai, Chien Yi Ho, Wen Shin Chang, Sheng Chi Chang, Long Bin Jeng, Yuhsin Tsai, Fuu Jen Tsai*, Da Tian Bau

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

23 Scopus citations

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors worldwide, for which the prevalence and mortality rates are very high in Taiwan. Caveolin-1 (CAV-1) is a main structural protein of caveolae and plays a regulatory role in signaling pathways and tumorigenesis. High expression of Cav-1 in mouse HCC is positively correlated with higher cell invasive capacity, but the contribution of CAV-1 genetic variants during HCC progression is still largely unknown. In this study, we investigated the contribution of CAV-1 variant to the risk of HCC from the analyses of DNA, RNA and proteins. Materials and Methods: We enrolled 298 patients with HCC and 298 cancer-free controls, frequency-matched by age and gender in this case-control study. Firstly, the associations of six single nucleotide polymorphisms (SNPs) of the Cav-1 gene at C521A (rs1997623), G14713A (rs3807987), G21985A (12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992) with HCC risk in a Taiwanese population were evaluated. Secondly, thirty HCC tissue samples with variant genotypes were tested to estimate for CAV-1 mRNA expression by real-time quantitative reverse transcription. Finally, the HCC tissue samples of variant genotypes were examined by western blotting to estimate their CAV-1 protein expression patterns. Results: There were significant differences between the HCC and control groups in the distributions of the CAV-1 G14713A genotypes (p=0.0124), and these carrying AG and AA genotypes had a higher risk for HCC, compared with those with the GG genotype (odds ratio=1.51 and 1.94, respectively). Patients with CAV-1 G14713A AG or AA genotype had higher levels of mRNA (p=0.0001) and protein (p=0.0019) than those with the GG genotype. Conclusion: Our multi-approach findings at the DNA, RNA and protein levels suggest that CAV-1 may play a critical role in HCC carcinogenesis, and serve as a target for HCC therapy.

Original languageEnglish
Pages (from-to)671-678
Number of pages8
JournalAnticancer Research
Volume33
Issue number2
StatePublished - 02 2013
Externally publishedYes

Keywords

  • Caveolin-1
  • Genotype
  • Hepatocellular carcinoma
  • Polymorphism
  • Real-time quantitative reverse transcription
  • Western blot

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