Knockdown of Sox-4 expression by RNAi induces apoptosis in adenoid cystic carcinoma

Abstract

4510

Adenoid cystic carcinoma (ACC) is one of the most common malignant neoplasms arising in salivary glands, but little is known of the molecular mechanisms involved in its pathogenesis. Large scale gene expression profiling analysis of ACC has revealed high expression of the Sox-4 gene, a member of a transcription regulator family involved in a wide range of developmental processes. While over-expression of Sox-4 gene has also been reported in several human cancers, the role of Sox-4 in tumorigenesis remains unclear. In this study, we examined the requirement of Sox-4 in ACC tumor growth using an RNAi approach. Using vector-based ShRNA system, the expression of sox-4 mRNA and protein levels in an ACC cell line (ACC3) were reduced to 20% of normal level 72 hrs after transfection. Strikingly, cell viability was significantly reduced by 51.1 ± 4.8% and the apoptotic rate increased dramatically from 12.4 ± 6.2% to 84.7 ± 2.5%. There was no evidence that Sox-4 altered cell cycle distribution in the ACC3 cells. In conclusion, our study suggests a critical contribution of Sox-4 in the maintenance of the malignant cell phenotype in ACC by inhibition of the apoptotic pathway, and identifies this gene as a novel target of therapy.