HAUSP gene acts as a tumor suppressor through p53 pathways in non-small cell lung cancers

Abstract

7202 Background: Recent studies have reported that herpesvirus-associated ubiquitin-specific protease (HAUSP) is a novel p53-interacting protein, and directly stabilizes the tumor suppressor p53 by deubiquitination. Therefore, HAUSP gene might play an important role in carcinogenesis, as one of the tumor suppressor genes in human cancers. In order to clarify this possibility in non-small cell lung cancers (NSCLCs), we evaluated the HAUSP gene expression and p53 gene status in relation to target genes of p53, such as p21 and bax. Methods: Eighty-four NSCLC patients were investigated. p53 gene status was evaluated by PCR-SSCP following sequencing. RT-PCR was performed to evaluate gene expression of HAUSP, p21 and bax. In addition, p21 and bax protein expression were confirmed by immunohistochemistry. Results: Fouty-six carcinomas (54.8%) had reduced expression of HAUSP, and 30 carcinomas (35.7%) had mutations of p53. Concerning tumor histology, HAUSP gene expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (P=0.002), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (P=0.029). There was no significant correlation between HAUSP gene expression and p53 gene status. Concerning expression of target genes of p53, p21 gene expression was significantly lower in the HAUSP-reduced tumors than in HAUSP-positive tumors (P=0.015). In addition, p21 gene expression was significantly lower in tumors with either reduced HAUSP expression or mutant p53 than in tumors with both positive HAUSP expression and wild type p53 (P =0.037). Furthermore, bax gene expression was also significantly lower in HAUSP-reduced tumors than in HAUSP-positive tumors (P=0.002). The bax gene expression was significantly lower in tumors with either reduced HAUSP expression or mutant p53 than in tumors with both positive HAUSP expression and wild type p53 (P =0.002). Conclusion: These results have suggested that the reduction of HAUSP gene expression might play an important role in carcinogenesis of NSCLCs through p53 pathways, by regulating gene expression of p21 and bax. No significant financial relationships to disclose.