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Cten, a COOH-terminal tensin-like protein with prostate restricted expression, is down-regulated in prostate cancer
1Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, The University of California-Davis, Sacramento, California 95817, USA. shlo@ucdavis.edu
Abstract:
Tensin is a signaling molecule that binds to actin filaments and localizes to focal adhesions. Recently, we have discovered that tensin represents a new gene family with related members that are expressed in a variety of tissues. In this study, we report the identification and characterization of a new COOH-terminal tensin-like molecule, cten. Human cten cDNA encodes a 715 amino acid sequence containing the Src homology 2 and phosphotyrosine-binding domains that are similar to the COOH termini of tensin molecules. Although cten is shorter and does not have the actin-binding domain found in other tensins, analysis of the genomic structure has suggested that cten is related to the tensin gene family. In addition, cten also localizes to focal adhesions. In contrast to other tensin members, cten expression is restricted to prostate and placenta by Northern blot analysis. Furthermore, examination of cten expression in prostate cancer/cell lines has revealed its down-regulation in tumor samples. Our studies have suggested that during evolution, cten has preserved its role in mediating signal transduction at focal adhesions through the Src homology 2 and phosphotyrosine-binding domains but has lost its function in binding to actin filaments. The evolutionary divergence has produced the first focal adhesion protein specifically expressed in the prostate and the placenta, which may be involved in preventing prostate tumor formation.
Insights
A new gene family member, cten, binds to focal adhesions and is expressed in the prostate and placenta. Its down-regulation in prostate cancer suggests a role in preventing tumor formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Tensin proteins are signaling molecules that bind actin filaments and localize to focal adhesions.
- Tensin represents a newly discovered gene family with diverse tissue expression.
- Focal adhesions are critical sites for cell adhesion and signal transduction.
Purpose of the Study:
- To identify and characterize a novel COOH-terminal tensin-like molecule, designated cten.
- To investigate the evolutionary relationship of cten to the tensin gene family.
- To determine the tissue-specific expression and potential role of cten in prostate cancer.
Main Methods:
- Human cten cDNA sequencing and analysis.
- Genomic structure analysis to infer evolutionary relationships.
- Northern blot analysis for tissue expression profiling.
- Examination of cten expression in prostate cancer cell lines.
Main Results:
- Human cten encodes a 715 amino acid protein with Src homology 2 and phosphotyrosine-binding domains, similar to tensins.
- cten lacks an actin-binding domain but localizes to focal adhesions.
- cten expression is predominantly restricted to the prostate and placenta.
- cten is significantly down-regulated in prostate cancer samples.
Conclusions:
- cten has evolved as a focal adhesion protein mediating signal transduction via its SH2 and PTB domains.
- Evolutionary divergence has resulted in cten losing actin-binding but gaining specific expression in prostate and placenta.
- The down-regulation of cten in prostate cancer suggests its potential role as a tumor suppressor, possibly preventing tumor formation.