Impact of TGIFLX Expression on the Regulation of BCL2 and BAX in Prostate Cancer Cell Line (LNCaP)

Abstract

Aims: The homeoprotein TGIFLX (transforming growth factor-β-induced factor 2-like, X-linked), which is essential in male reproduction and development and likely oncogenic when aberrantly expressed in prostate. We have previously shown an aberrant expression of TGIFLX in the majority of human prostate tumors. However, mechanism by which TGIFLX acts in prostate cancer is unknown. The aim of this study was to investigate the effects of overexpression of wild-type TGIFLX (wt-TGIFLX) on LNCaP, human prostate adenocarcinoma cells. Study Design: As a prospective study, we used adenovirus expression system for evaluation of TGIFLX expression effects on mammalian cells. Place and Duration of Study: Medical Genetics Department, Tehran University of Medical Sciences (TUMS), between December 2009 and July 2012. Methodology: We cloned entire coding sequence of TGIFLX gene into adenovirus and subsequently LNCaP cells were transfected with the recombinant virus harboring TGIFLX cDNA or control. The TGIFLX expression was confirmed by microscopic analysis and RT-PCR technique. Following molecular cloning and characterization of TGIFLX transcription factor, we then studied the effects of overexpression of TGIFLX in LNCaP cells on mRNA expression of BAX and BCL2 genes. Results: Our results showed that overexpression of TGIFLX downregulated BCL2 gene (P<0.05) and upregulated BAX gene (P<0.05) at transcript level. Our results suggested that TGIFLX could be a tumor suppressor gene and might be involved in initiation and/or development. Conclusion: TGIFLX can play a role as a transcriptional modulator of the genes involved in cell cycle pathway. But still more investigations are necessitated for clarifying this claim.