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High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma

Leukemia volume 17, pages 1880–1890 (2003)Cite this article

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.

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Acknowledgements

This research was supported by the Swedish Cancer Society, the Swedish Medical Research Council, and the Alice and Knut Wallenberg Foundation. We thank Drs Ken Mackie, Department of Anaesthesiology, University of Washington, Seattle, WA, USA for generously providing antibodies to cannabinoid receptors and the AtT20 CB1-transfected cell line and Dr Christian Bastard, Molecular Biology Laboratory and EMI 9906-IRFMP, Centre Henri Becquerel, Rouen, France for providing the Rec 1 cell line. We are grateful to Dr Karin Dahlman-Wright and Hui Gao, Karolinska Institutet, Department of Biosciences for help and support to the users of the Affymetrix core facility and to Fiona Brew and Camilla Ejdestig, Affymetrix for the workshops on data mining. We thank Pia Lennartsson for skilful technical help.

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Authors and Affiliations

  1. Clinical Research Center, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    T C Islam, A C Asplund, J M Lindvall & C I E Smith

  2. Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    L Nygren, B Christensson & B Sander

  3. Department of Biosciences, Novum, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    J Liden

  4. Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    E Kimby

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Correspondence to B Sander.

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Islam, T., Asplund, A., Lindvall, J. et al. High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma. Leukemia 17, 1880–1890 (2003). https://doi.org/10.1038/sj.leu.2403057

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