Abstract

AbstractPhosphatase and tensin homolog deleted on chromosome 10 (PTEN), a multifunctional tumor suppressor, has been shown to play a regulatory role in cell migration. Dictyostelium discoideum cells lacking PTEN exhibited impaired migration toward chemoattractant gradients. In the present study, we investigated the involvement of PTEN in chemotaxis of mammalian cells by examining PTEN-null Jurkat T cells. We observed that, in contrast to observations made in D discoideum, PTEN-null Jurkat T cells exhibited potent chemotactic responses to the chemokine stromal cell–derived factor 1α (SDF-1α), indicating that PTEN was not requisite for CXC chemokine receptor 4 (CXCR4)–mediated chemotaxis of Jurkat cells. Conversely, reconstitution of PTEN in Jurkat cells by using a tetracycline (Tet-on)–inducible expression system down-regulated CXCR4-mediated chemotaxis. Furthermore, we established the lipid phosphatase activity of PTEN as essential for its inhibitory effect on chemotaxis. In addition, using PTEN-expressing T-cell lines and primary T cells, we demonstrated that down-regulation of PTEN expression with vector-based small interfering RNAs (siRNAs) enhanced CXCR4-mediated chemotaxis. Based on these results, we conclude that PTEN expression negatively regulates chemotaxis of lymphoid mammalian cells via its lipid phosphatase activity. Our findings may account for the reported increase in metastatic activity of PTEN-null tumor cells.

Highlights

  • Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), one of the most frequently mutated or deleted tumor suppressor genes in human cancers,[12,13,14] has been shown to play an important role in regulating cell migration

  • Several previous studies have reported that Jurkat cells were PTEN deficient;[22,28,29,30] there were reports showing that Jurkat cells expressed wild-type PTEN.[31]

  • We investigated the naturally occurring PTEN-null human Jurkat T-cell line to characterize the involvement of PTEN in chemotaxis of mammalian cells

Read more

Summary

Introduction

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), one of the most frequently mutated or deleted tumor suppressor genes in human cancers,[12,13,14] has been shown to play an important role in regulating cell migration. While Fox et al[20] demonstrated that PTENϩ/Ϫ mouse B lymphocytes exhibited enhanced chemotactic responses to chemokine stromal cell– derived factor 1␣ (SDF-1␣), Anzelon et al[21] reported that the conditional deletion of PTEN from mouse B cells resulted in a general impairment in chemotaxis induced by SDF-1␣ and Blymphocyte chemoattractant (BLC). These discrepancies point to the necessity to further elucidate the role of PTEN in regulating the chemotaxis of mammalian cells. Our results may serve to invite more extensive and straightforward approaches to investigate the antimetastatic function of PTEN in human malignancy

Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.