The helix‐loop‐helix protein Id2 is expressed differentially and induced by myc in T‐cell lymphomas

Abstract

BACKGROUND. Inhibitor of DNA binding 2 (Id2), a helix‐loop‐helix protein of the inhibitor of differentiation (ID) family, is involved in hematopoiesis, mainly through interaction with the E‐family of transcription factors. Recent studies have shown that Id2 is overexpressed in some types of B‐cell lymphoma, including classical Hodgkin lymphoma. The authors of the current study hypothesized that Id2 also is overexpressed in T‐cell lymphomas. METHODS. By using reverse‐transcriptase polymerase chain reaction (RT‐PCR) and Western blot analyses, high Id2 messenger RNA (mRNA) and protein levels, respectively, were detected in all 4 T‐cell anaplastic large cell lymphoma (ALCL) cell lines that were tested. RESULTS. Immunohistochemistry results indicated that Id2 was expressed strongly in 21 of 27 (78%) ALCL tumors (79% anaplastic lymphoma kinase [ALK]‐negative and 75% ALK‐positive), in 5 of 10 (50%) extranodal natural killer/T (NK/T)‐cell lymphomas of the nasal type, in 2 of 8 (25%) cutaneous ALCLs, in 2 of 9 (22%) enteropathy type T‐cell lymphomas, in 1 of 5 (20%) peripheral T‐cell lymphomas not otherwise specified, and in 1 of 8 (13%) T‐cell prolymphocytic leukemias. Other types of T‐cell lymphoma were negative for Id2. Because it is known that myc is expressed in ALCL, myc was inhibited selectively in 2 ALCL cell lines, resulting in a concentration‐dependent decrease in Id2 mRNA and protein levels. Conversely, forced expression of myc in HEK 293T cells using an myc/green fluorescent protein adenoviral vector resulted in Id2 up‐regulation. CONCLUSIONS. Taken together, the current data suggest that Id2 commonly is overexpressed in highly proliferative T‐cell lymphomas, and its expression may result from transcriptional activation of myc in these tumors. Cancer 2008. © 2007 American Cancer Society.

Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

“…We revealed in LyP cases an aberrant expression of Fra2 and, in agreement with recent observations (19), Id2. These data support the view of a pathogenetic link between these disease entities.…”

“…1C and Table S1). We detected high expression of Fra2 and, in accordance with previously published data (19), of Id2 in all 10 t(2;5)-positive ALCL cases, and in 9/15 (Fra2) and 15/15 (Id2) t(2;5)-negative ALCL tumor samples. In contrast, Fra2 was not detected, and Id2 was expressed at a much lower level in only a subset of lymphoid cells in normal lymphoid tissue, including nonmalignant lymphoid cells present in all ALCL samples and in samples from activated human palatine tonsil, thymus, and spleen ( Fig.…”

TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

“…Overexpression of Id proteins in embryonic-derived fibroblasts facilitates cell cycle S-phase under serum-deprived conditions [34], where Id-1 has been reported to induce the proliferation of cochlear sensory epithelial cells via the NF-kappaB/cyclin D1 pathway [35]. Furthermore, various cancer cell lines appear to require Id-1 and Id-2 expression for their growth, survival, and metastasis via regulation of p53 and PI3K/Akt/NF-kappaB signaling pathways in a similar fashion to that described for Twist-1 and Dermo-1 [36][37][38][39][40]. More recently, Id-1 has been shown to mediate long-term repopulating hematopoietic stem cell maintenance and inhibit myeloid differentiation [41,42].…”

Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

“…The overexpression of Id2 in ALCL, PTCL and multiple other types of T cell lymphomas, and its induction by Myc, supported this hypothesis [105]. In mouse models expressing an Id2 transgene, there is a developmental block at early steps of T cell development, accompanied by hyperproliferating T cell lymphomas in most mice [106].…”