Identification and characterization of the human testes-specific protease 50 gene promoter.

Testes-specific protease 50 (TSP50) has been identified as one of the testis-specific proteins that is expressed at high levels in approximately 92% of human breast cancer samples, making it an attractive molecular marker and a potential target for diagnosis and therapy. However, little is known about the transcriptional mechanisms controlling TSP50 gene expression. In the present study, we have characterized the 5' regulatory region of the TSP50 gene in order to understand the molecular mechanisms regulating its expression.

Screening of single-chain variable fragments against TSP50 from a phage display antibody library and their expression as soluble proteins.

A novel gene, testes-specific protease 50 (TSP50), is abnormally activated and differentially expressed in most patients with breast cancer, suggesting it as a novel biomarker for this disease. The possibility that TSP50 may be an oncogene is presently under investigation. In this study, the single-chain variable fragments (scFvs) against TSP50 were panned from a phage display antibody library using TSP50-specific peptide, pep-50, as a target antigen.

Localization and expression of TSP50 protein in human and rodent testes.

Objectives: To present our recent observations obtained from the continuing characterization of the TSP50 gene pertaining to its evolutionary importance and behavior in human testicular germ cell tumors. Previous studies have reported that expression of the human TSP50 gene is testes specific. Its product is similar to many serine proteases but possesses its own unique features.

Partially unspliced and fully spliced ELF3 mRNA, including a new Alu element in human breast cancer.

Using modified representational difference analysis, a DNA fragment (GC3) was isolated as a difference between a breast cancer and a normal cell line from the same patient. GC3 proved to be a fragment of intron 7 of the ELF3 gene, an ets family transcription factor, amplified in the breast cancer cell line. Using genomic walking technology, a new Alu (Alu(kwd)) was found downstream of GC3 in an antisense position between nt 8762 and nt 8763 within intron 8 of the ELF3 gene.

WTH3, a new member of the Rab6 gene family, and multidrug resistance.

The WTH3 gene was obtained by a DNA fragment isolated by the methylation-sensitive representational difference analysis technique due to its hypermethylation in the human multidrug resistant (MDR) breast cancer cell line MCF7/AdrR. The WTH3 gene product is 89% and 91% identical to the human Rab6 and Rab6c proteins, but possesses an elongated C-terminal region which contains 46 extra amino acids. Nevertheless, we consider the WTH3 gene a new member of the Rab6 gene family.

TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells.

Initial studies have identified TSP50 as a human testes-specific gene that is demethylated in breast cancer. In this study, we will present new data related to the TSP50 gene. We have found that the TSP50 gene product shares a similar enzymatic structure with many serine proteases.

Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model.

Homeostasis of the extracellular matrix (ECM) of tissues is regulated by controlling deposition and degradation of ECM proteins. The breakdown of ECM is essential in blastocyst implantation and embryonic development, tissue morphogenesis, menstrual shedding, bone formation, tissue resorption after delivery, and tumor growth and invasion. TGF-beta family members are one of the classes of proteins that actively participate in the homeostasis of ECM.