1. High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma.
- Author
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Islam TC, Asplund AC, Lindvall JM, Nygren L, Liden J, Kimby E, Christensson B, Smith CI, and Sander B
- Subjects
- Adolescent, Adult, Aged, Burkitt Lymphoma genetics, Burkitt Lymphoma metabolism, Burkitt Lymphoma pathology, Case-Control Studies, Cell Division, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Child, Cyclin D1 genetics, Cyclin D1 metabolism, DNA, Neoplasm analysis, DNA, Neoplasm genetics, Down-Regulation, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Leukemia, B-Cell genetics, Leukemia, B-Cell metabolism, Leukemia, B-Cell pathology, Lymphoma, Mantle-Cell metabolism, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Neoplasm Proteins metabolism, Oligonucleotide Array Sequence Analysis, RGS Proteins metabolism, RNA, Messenger analysis, RNA, Neoplasm genetics, Receptors, Cannabinoid, Receptors, Drug metabolism, Reverse Transcriptase Polymerase Chain Reaction, Cell Transformation, Neoplastic genetics, Lymphoma, Mantle-Cell genetics, Neoplasm Proteins genetics, RGS Proteins genetics, Receptors, Drug genetics
- Abstract
Mantle cell lymphoma (MCL) is a moderately aggressive B-cell lymphoma that responds poorly to currently used therapeutic protocols. In order to identify tumour characteristics that improve the understanding of biology of MCL, analysis of oligonucleotide microarrays were used to define specific gene expression profiles. Biopsy samples of MCL cases were compared to reactive lymphoid tissue. Among genes differentially expressed in MCL were genes that are involved in the regulation of proliferation, cell signalling, adhesion and homing. Furthermore, some genes with previously unknown function, such as C11orf32, C2orf10, TBC1D9 and ABCA6 were found to be differentially expressed in MCL compared to reactive lymphoid tissue. Of special interest was the high expression of the cannabinoid receptor 1 (CB1) gene in all MCL cases analysed. These results were further confirmed at the cellular and protein level by immunocytochemical staining and immunoblotting of MCL cells. Furthermore, there was a reduced expression of a regulator of G protein signalling, RGS13 in all MCLs, with a complete absence in the majority of cases while present in control lymphoid tissue. These results were further confirmed by PCR. Sequencing of the RGS13 gene revealed changes suggesting polymorphisms, indicating that downregulation of the expression of RGS13 is not related to mutations, but may serve as a new specific marker for MCL. Moreover, comparison between individual cases of MCL, revealed that the CCND1 gene appears to be differently expressed in MCL cases with high vs low proliferative activity.
- Published
- 2003
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