The helix-loop-helix protein Id2 is expressed differentially and induced by myc in T-cell lymphomas.
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.
Cotta
Claudiu V
CV
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Leventaki
Vasiliki
V
Atsaves
Vassilis
V
Vidaki
Athina
A
Schlette
Ellen
E
Jones
Dan
D
Medeiros
L Jeffrey
LJ
Rassidakis
George Z
GZ
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology; D017731:Lymphomatoid Papulosis / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger