Receptor-Ck controls the expression of Bcl-2 and cyclin D genes

• Published in: Leukemia research Vol. 22; no. 8; pp. 671 - 675
• Main Authors: Kaul, D, Kaur, M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.08.1998
• Subjects: Base Sequence; Biological and medical sciences; Cyclin D; Cyclins - genetics; Gene Expression Regulation - physiology; Genes, bcl-2; Hematologic and hematopoietic diseases; Humans; In Vitro Techniques; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes - metabolism; Medical sciences; Oligodeoxyribonucleotides; Receptors, Lipoprotein - physiology; Signal Transduction - physiology; Tropical medicine; Human; Immunocytochemistry; Pathogenesis; Cyclin; Homeostasis; Lipids; Malignant hemopathy; Gene expression; Cyclin D1; In vitro; Cholesterol; Pathology; Myeloproliferative syndrome; Chronic; Regulation(control); C-Onc gene; Chronic myelocytic leukemia; Immunoblotting assay; Lymphocyte; Protooncogene; Apoptosis; Biological receptor
• ISSN: 0145-2126
• DOI: 10.1016/S0145-2126(98)00012-5

By making use of receptor-Ck positive lymphocytes (from normal human subjects) as well as receptor-Ck negative lymphocytes (from untreated chronic myeloid leukemic (CML) patients) as cellular models, we were able to show that receptor-Ck-dependent signalling is involved in the regulation of genes coding for Bcl-2 and cyclin D. Further, experiments directed to resolve the mechanism by which this receptor regulates these genes revealed that receptor-Ck, upon activation by cholesterol, initiates the cleavage of a 125 kDa cytoplasmic protein leading to the generation of a 47 kDa factor having specific affinity for genomic sterol regulatory element (SRE)/SRE-like sequence present in the promoter region of genes coding for Bcl-2 and cyclin D. Based upon these observations, we propose that the inability of leukemic cells to express receptor-Ck is responsible for the deregulated over-expression of genes coding for Bcl-2 and cyclin D and this phenomenon may be of importance in understanding leukemic haematopoiesis.