Disease relevance of TMSB10

• These results strongly suggest that Thr20 is specifically required for actin sequestration by TB10 in ovarian cancer cells [1].
• Therefore, we conclude that thymosin beta-10 can be considered as a new progression marker for human cutaneous melanoma [2].
• However, in the HTB-10 neuroblastoma, retinoic acid caused a reduction in the level of thymosin beta 10 [3].
• We have recently shown that the TB10 gene is overexpressed in human thyroid carcinoma cell lines and tissues, particularly in undifferentiated thyroid carcinomas, but expressed at an undetectable level in normal thyroid cells [4].
• Our analyses showed a TB10 positive staining in all human thyroid carcinomas particularly in the anaplastic histotypes, whereas no TB10 immunostaining was observed in normal thyroid, in adenomas and the majority of the goiters [5].

High impact information on TMSB10

• Differential expression of thymosin beta-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis [6].
• The reduced expression of thymosin beta-10 may contribute to the senescent phenotype by reducing EC plasticity and thus impairing their response to migratory stimuli [6].
• ISH performed on human malignant tumors revealed strong thymosin beta-10 expression in tumor blood vessels [6].
• These EC expressed senescence-associated neutral beta-galactosidase and, in contrast to adventitial microvessel endothelium, exhibited weak staining for thymosin beta-10 [6].
• Thymosin beta-10 gene overexpression correlated with the highly malignant neoplastic phenotype of transformed thyroid cells in vivo and in vitro [7].

Chemical compound and disease context of TMSB10

• 3. To examine further the possibility that the trophic actions of retinoic acid upon expression of the thymosin beta 10 gene involved retinoid receptors, neuroblastoma cells were transiently transfected with an expression vector encoding the nuclear retinoic acid receptor (alpha) protein [8].
• In vivo results showed that the steady-state level of thymosin beta10 mRNA is up-regulated in the thyroid gland of propylthiouracil-fed rats in parallel with follicular cell proliferation: iodide administration to goitrous rats, which induced a marked involution of thyroid hyperplasia, reduced the mRNA level of thymosin beta10 [9].

Biological context of TMSB10

• To identify the critical residues responsible for TB10-mediated apoptosis, we used a series of computational methods [1].
• These results, together with primer extension experiments, suggest that the two thymosin beta 10 mRNAs are transcribed from the same gene through a combination of differential promoter utilization and alternative splicing [10].
• The conserved 17LKKTET(22 motif region of TB10 was tested by Ala and Ser scanning mutagenesis using computational and biochemical methods, and 12 mutants were transfected into cancer cell lines and tested for their effects on growth arrest [1].
• Immunohistochemical analysis showed that the protein was present in differentiating spermatids, suggesting that the testis-specific thymosin beta 10 mRNA is translated in haploid male germ cells [10].
• Previously, we demonstrated that overexpression of TB10 in ovarian tumor cells increased the rate of cell death [11].

Anatomical context of TMSB10

• By means of immunohistochemistry we could show that thymosin beta-10 (TMSB10), upregulated in tumor cell lines, is expressed in human pancreatic carcinoma, but not in non-neoplastic pancreatic tissue, suggesting a role for TMSB10 in the carcinogenesis of pancreatic carcinoma [12].
• Recently, we have demonstrated the overexpression of thymosin beta-10 (TB10) in rat thyroid transformed cell lines and in human thyroid carcinoma tissues and cell lines [13].
• Overexpression of the TB10 gene was detected in all of the neoplastic tissues and cell lines compared to the respective normal tissues [13].
• Immunoblot analysis using specific antibodies showed that the thymosin beta 10 protein synthesized in adult testis was identical in size to that synthesized in brain [10].
• Cloning and characterization of a testis-specific thymosin beta 10 cDNA. Expression in post-meiotic male germ cells [10].

Associations of TMSB10 with chemical compounds

• The retinoic acid-responsive thymosin beta-10 gene is known to be developmentally regulated in the human brain [14].
• Genes coding for pyruvate kinase M2 isozyme, clathrin assembly proteins, calmodulin, fibronectin, laminin, thymosin beta-10, and many others were upregulated as NT2/D1 cells differentiated into neurons [15].
• The most abundant transcripts included ribosomal and mitochondrial proteins, of which most were upregulated in the tumours, as were other widely expressed genes including transcription factors, signalling molecules (serine/threonine protein kinases), thymosin beta 10 and collagenase I [16].
• These results clearly demonstrate that NF-YB and thymosin beta-10 are specific cellular binding proteins of HMN-154 and that this shared region is necessary for the binding to HMN-154 [17].
• A luteolytic dose of prostaglandin F2 alpha (500 micrograms/rat) had little impact on ovarian thymosin beta 10 gene expression [18].

Other interactions of TMSB10

• Most frequent was the loss of 1 copy of TMSB10, observed in 11 of 12 SCV patients, followed by loss of CTNNB1 and BCL2, which occurred in 7 of 12 patients [19].
• Among the 63 developmentally regulated genes, four exhibited the highest levels of expression (TMSB10, CTNNA1, NMP1, and CX3CL1) [20].
• However, while thymosin beta-10 mRNA was undetectable (by northern blot analysis) in adult human brain, levels of thymosin beta-4 mRNA, although greatly reduced, were still present [14].
• The upregulated genes included CD44, high mobility group protein-I, thymosin beta-10 and 27-kD heat shock protein, while the downregulated genes included NM23-H1, all of which are thought to be associated with the development or progression of carcinoma in the liver or other organs [21].
• The expression of Tmsb10, S100a6 and Anxa2 coincided with heavy proteinuria [22].

Analytical, diagnostic and therapeutic context of TMSB10

• Furthermore, Northern blot analysis showed that also in freshly harvested human melanocytic lesions thymosin beta-10 was differentially expressed [2].
• Human fetal brain expresses high levels of a polypeptide identified by protein biochemistry and molecular cloning as thymosin beta 10 [3].
• Finally, the thymosin beta-10 gene was located on chromosome 2q37 by fluorescence in situ hybridization analysis [7].
• HPLC analysis also indicated the presence in the ovary of thymosin beta 4, a variant member of the same protein family; in general, ovarian thymosin beta 4 levels fluctuated in a manner reciprocal to that exhibited by thymosin beta 10 [18].
• C-terminal truncation of thymosin beta10 by an intracellular protease and its influence on the interaction with G-actin studied by ultrafiltration [23].

References