Disease relevance of TEGT

• An examination of the TSS of some genes, such as TEGT and GAPD, using 5' RACE revealed that the predicted TSSs are actually found in human gastric cancer cells and that several TSSs differ depending on the specific gastric cell line [1].
• Taken together, our results indicate that the human BI-1 gene contains the potential to serve as a prostate cancer expression marker and as a potential target for developing therapeutic strategies for prostate cancer [2].
• Furthermore, quantitative RT-PCR on RNAs derived from five benign prostate hyperplasia (BPH) samples showed no significant difference in BI-1 expression as compared to normal epithelial prostate tissue [2].
• Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma [3].
• BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading [3].

High impact information on TEGT

• When overexpressed in mammalian cells, BI-1 suppressed apoptosis included by Bax, etoposide, staurosporine, and growth factor deprivation, but not by Fas (CD95) [4].
• BI-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax [4].
• By exploiting this phenotype, we have identified a novel human Bax inhibitor, BI-1 [4].
• BI-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments and is predominantly localized to intracellular membranes, similar to Bcl-2 family proteins [4].
• Chemical induction of resistance to Bgh by soil drench treatment with 2,6-dichloroisonicotinic acid led to down-regulation of the expression level of BI-1 [5].

Biological context of TEGT

• The TEGT gene maps to human chromosome 12q12-q13 and belongs to a syntenic group, which is conserved in human, mouse, and rat [6].
• Two different transcripts of TEGT occur, which are due to alternative usage of two polyadenylation sites [6].
• TEGT is able to inhibit the expression of Bax, which is known to promote apoptosis [7].
• To determine the function of BI-1 in vitro, human PC-3, LNCaP, and DU-145 prostate carcinoma cells were transfected with small interfering double-strand RNA (siRNA) oligonucleotides against the BI-1 gene leading to a specific down-regulation of BI-1 expression [2].
• Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells [2].

Anatomical context of TEGT

• In situ hybridization experiments on prostate sections also revealed that BI-1 expression is mainly restricted to epithelial cells [2].
• In addition, it was demonstrated that BI-1 expression is down-regulated in stromal cells as compared to matched normal epithelial cells of the prostate [2].
• Immunofluorescence of cells transiently expressing haemagglutinin-tagged hTEGT localized the protein mainly to the endoplasmic reticulum [8].
• (iii) The protein appeared to associate strongly with other intracellular molecules since haemagglutinin-tagged hTEGT was extracted poorly from transiently transfected HeLa cells [8].
• (i) In vitro translation of hTEGT in reticulocyte lysates required the presence of microsomes for efficient synthesis, suggesting that hTEGT must target to the endoplasmic reticulum to be translated [8].

Associations of TEGT with chemical compounds

• Among them, we selected two candidates the TEGT BI-1 (testis enhanced gene transcript Bax Inhibitor-1) and the CD63 gene in order to further confirm their differential expression under tamoxifen effects [7].
• BI-1 appears to suppress cell death induced by mitochondrial dysfunction, reactive oxygen species or elevated cytosolic Ca(2+) levels [9].

Other interactions of TEGT

• Inhibition of mitochondrial membrane permeabilization by overexpression of Bcl-2 or expression of the cytomegalovirus-encoded protein vMIA (viral mitochondrial inhibitor of apoptosis), which acts as a specific Bax inhibitor, prevented the induction of cell death by the combination of hTERT depletion and chemotherapeutic agents [10].
• Novel genes involved in the regulation of apoptosis were found for the first time to be up-regulated by gonadotrophin stimulation, including: BAX inhibitor-1, granulysin and apoptosis repressor with caspase recruitment domain (ARC) [11].
• The mechanism for these BI-1-associated functions involves the expression of heme oxygenase-1 (HO-1) through nuclear factor erythroid 2-related factor 2 [12].

Analytical, diagnostic and therapeutic context of TEGT

• Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) on intact RNAs from 17 paired laser-captured microdissected epithelial tissue samples confirmed up-regulated BI-1 expression in 11 of 17 prostate tumors [2].
• The overexpression of Bax inhibitor-1 (BI-1) in prostate carcinoma and prostate cancer cell lines was confirmed by using Northern blot and Western blot analyses [2].
• However, sequence analysis of lung BI-1 revealed unique nucleotides starting 29 bases upstream of the ATG initiation codon and extending to the 5' end of lung-derived BI-1 cDNA compared to the original transcript from the testis [13].
• Protein expressions of p53, Bcl-2, and Bax, as detected by immunohistochemistry, were not associated with BI-1 gene expression [3].

References