Disease relevance of TSC22D1

• On immunostaining of the transfected cells, almost every cell that expressed TSC-22 tagged with influenza virus haemagglutinin exhibited the morphology of an apoptotic cell [1].
• The cDNA array analysis of differential expression of the TGFbeta superfamily and functionally related genes between patient-matched noncancerous prostate (NP) and prostate cancer (PC) bulk tissue specimens highlighted two genes, namely TGFbeta-stimulated clone-22 (TSC-22) and Id4 [2].
• We estimated the frequency of the -396 A/G polymorphism of the TSC-22 gene with an Alu I-Restriction fragment length polymorphism (RFLP) method in 498 Japanese subjects with type 2 diabetes mellitus [3].
• The differential expression of TSC-22 gene was confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II-IV and three samples of normal brain [4].
• Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors [4].

High impact information on TSC22D1

• We constructed an expression vector containing sense- or antisense-oriented human TSC-22 cDNA under the transcriptional control of the SR alpha promoter [5].
• The ability of PPARgamma to induce TSC-22 was not dependent on an intact TGF-beta1 signaling pathway and was specific for the gamma isoform [6].
• Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22 [6].
• Furthermore, transfection with a dominant negative TSC-22 in which both repressor domains were deleted was able to reverse the p21 induction and growth inhibition caused by activation of either the PPARgamma or TGF-beta pathways [6].
• TSC-22 is member of a family of leucine zipper containing transcription factors with repressor activity [6].

Biological context of TSC22D1

• TSC-22 gene was composed of three exons and its length was approximately 5.5 kb including 2.9 kb promoter region [7].
• These observations suggest that up-regulation of TSC-22 mRNA by TGF-beta 1 is achieved by mRNA stabilization, but not by transcriptional activation [7].
• The cellular events characteristic of apoptosis, chromatin condensation and DNA fragmentation were observed only in cells transfected with a TSC-22 expression vector [1].
• Protection against cell death by the transfection of a TSC-22 expression vector was also offered by Ac-DEVD-CHO addition [1].
• HSC-39 cells transfected with a TSC-22 expression vector showed a significant decrease in cell viability compared with those transfected with a control vector [1].

Anatomical context of TSC22D1

• We have identified transforming growth factor-simulated clone-22 (TSC-22) as a target gene of both pathways in intestinal epithelial cells [6].
• Likewise, PC cell lines do not show detectable TSC-22 protein expression as shown by immunoblotting [2].
• Conversely, lack of TSC-22 seems to be a hallmark of malignant transformation of the prostate epithelium [2].
• We have recently isolated TSC-22 (transforming growth factor-beta-stimulated clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a human salivary gland cancer cell line, TYS [8].
• CONCLUSION: TSC-22 protein is expressed in astrocytes, but not in macrophage/microglial cells [9].

Associations of TSC22D1 with chemical compounds

• The repressor activity of TSC-22 appears sensitive for promoter architecture, but not for the histone deacetylase inhibitor trichostatin A [10].
• Over-expression of TSC-22 (TGF-beta stimulated clone-22) markedly enhances 5-fluorouracil-induced apoptosis in a human salivary gland cancer cell line [8].
• Furthermore, the induction of TSC-22 by vesnarinone was inhibited by treatment with cycloheximide [11].

Co-localisations of TSC22D1

• Immunohistochemical analysis showed that TSC-22 protein expression in NP is restricted to the basal cells and colocalizes with the basal cell marker cytokeratin 5 [2].

Regulatory relationships of TSC22D1

• Although originally TSC-22 was isolated as a TGF-beta-inducible gene, TSC-22 promoter was not activated by the enhanced TGF-beta signaling [7].
• In this study, we examined the in vivo chemosensitivity of TSC-22-expressing TYS cells [12].

Other interactions of TSC22D1

• Cells transfected with wild-type TSC-22 exhibited reduced growth rates and increased levels of p21 compared with vector-transfected cells [6].
• Interestingly, both TSC-22 and THG-1 have transcriptional repressor activity when fused to a heterologous DNA-binding domain [10].
• These findings suggest that the TSC-22 gene (-396) A allele is associated with an increasing risk of the diabetic nephropathy [3].
• Collagen IIA was also induced by seven genes, the most potent being transforming growth factor beta (TGFbeta)-stimulated protein TSC22, vascular endothelial growth factor (VEGF) and splicing factor 3a [13].
• Immunohistochemical analysis of TSC-22 and GFAP expression with the use of anti-human-TSC-22- and anti-human-GFAP-antibodies was performed on histological slides of astrocytic tumors [9].

Analytical, diagnostic and therapeutic context of TSC22D1

• Accordingly, TSC-22 immunohistochemistry may prove to be a diagnostic tool for discriminating benign lesions from malignant ones of the prostate [2].
• Verification of their mRNA expression by real-time PCR in patient-matched NP and PC bulk tissue, in laser-captured pure epithelial and cancer cells and in NP and PC cell lines confirmed TSC-22 underexpression, but not Id4 overexpression, in PC and in human PC cell lines [2].
• It was found by TUNEL assay that TSC-22-expressing TYS tumors were induced to undergo apoptosis by 5-FU treatment [12].
• Furthermore, intraperitoneal injection of 5-fluorouracil (5-FU) markedly inhibited the growth of the TSC-22-expressing TYS tumors, but did not affect the growth of control tumors [12].
• The expression of TSC-22 was up-regulated within a few hours after treatment with vesnarinone and was continued for 3 days [11].

References