TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas.
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.
Young
Ryan M
RM
Department of Dermatology, Charles C. Gates Regenerative Medicine and Stem Cell Program, University of Colorado Denver Health Sciences Center, Aurora, CO 80045, USA.
Polsky
Avital
A
Refaeli
Yosef
Y
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016271:Proto-Oncogene Proteins c-myc; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516653:Ptpn2 protein, mouse