TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas.

Abstract

We sought to determine the contributions of protein tyrosine phosphatases (PTPs) to the pathogenesis of B-cell lymphomas. We found that T-cell PTP (TC-PTP) was overexpressed in transformed B cells. We hypothesized that TC-PTP may be a tumor-promoting gene that is regulated by MYC overexpression in B cells. Knockdown of TC-PTP in murine tumors resulted in decreased cell viability in vitro because of an arrest in the G(1) phase of the cell cycle. Furthermore, cells with reduced TC-PTP expression were unable to either engraft or expand in vivo. Taken together, these data indicate that TC-PTP is required for B-cell tumor maintenance. Our data also suggested a correlation between TC-PTP expression and MYC overexpression. To investigate this further, we used malignant murine B cells that contain a doxycycline-repressible MYC transgene. We found that repression of MYC overexpression with doxycycline reduced TC-PTP expression. Moreover, enforced expression of TC-PTP showed partial rescue of the expansion of tumor cells after suppression of MYC overexpression. These results suggest that MYC overexpression induces TC-PTP overexpression, which in turn promotes tumor proliferation, implicating TC-PTP as an important effector of the MYC-driven proliferation program in B-cell lymphomas. Thus, TC-PTP may be a suitable molecular target for the treatment of B-cell lymphomas.

• Authors: Ryan M Young, Avital Polsky, Yosef Refaeli
• Journal: Blood (Blood) Vol. 114 Issue 24 Pg. 5016-23 (Dec 03 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19755676 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-myc
• Protein Tyrosine Phosphatase, Non-Receptor Type 2
• Ptpn2 protein, mouse

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lymphoma, B-Cell (genetics, metabolism)
• Mice
• Mice, Transgenic
• Protein Tyrosine Phosphatase, Non-Receptor Type 2 (genetics, metabolism)
• Proto-Oncogene Proteins c-myc (genetics)
• Reverse Transcriptase Polymerase Chain Reaction