Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies.
Our laboratory has recently discovered a novel candidate oncogene, MCT-1, amplified in human T-cell lymphoma and mapped to chromosome Xq22-24. This region is amplified in a subset of primary B-cell non-Hodgkin lymphoma (NHL), suggesting that increased copy number of a gene(s) located in this region confers a growth advantage to some primary human lymphomas. We examined a diverse panel of lymphoid malignancies for the expression of MCT-1. We demonstrated that there are significantly increased levels of MCT-1 protein in a panel of T-cell lymphoid cell lines and in non-Hodgkin lymphoma cell lines. Furthermore, we identified a subset of primary diffuse large B-cell lymphomas that exhibited elevated levels of MCT-1 protein. Interestingly, all transformed follicular lymphomas in our study demonstrated elevated protein levels of MCT-1. There was no detectable MCT-1 protein in leukemic cells from patients with chronic lymphocytic leukemia or in any healthy lymphoid tissue examined. Lymphoid cell lines overexpressing MCT-1 exhibited increased growth rates and displayed increased protection against apoptosis induced by serum starvation when compared with matched controls. We found that MCT-1-overexpressing cells show constitutively higher levels of phosphorylated PKB/Akt protein, especially under serum starvation. Activation of survival pathways may be an additional function of the MCT-1 gene. Our data suggest that high levels of MCT-1 protein may be associated with a high-risk subset of lymphoid neoplasms and may further support the potential role of MCT-1 in promoting human lymphoid tumor development.
Shi
Bo
B
Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.
Hsu
Hsin-Ling
HL
Evens
Andy M
AM
Gordon
Leo I
LI
Gartenhaus
Ronald B
RB
D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology* / Q000473:pathology; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013601:T-Lymphocytes / Q000737:chemistry / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; C115081:MCTS1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt