Effects of overexpression of HBP1 upon growth and differentiation of leukemic myeloid cells

• Published in: Leukemia Vol. 19; no. 11; pp. 1958 - 1968
• Main Authors: YAO, C. J, WORKS, K, ROMAGNOLI, P. A, AUSTIN, G. E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.11.2005; Nature Publishing Group
• Subjects: Annexin V; Antibodies; Apoptosis; Biological and medical sciences; c-Myb protein; c-Myc protein; Cell culture; Cell cycle; Cell Differentiation; Cell growth; Cell Proliferation; Cell Transformation, Neoplastic; Cyclin D1; Differentiation; FasL protein; Gene expression; Gene Expression Profiling; Hematologic and hematopoietic diseases; Hemoglobin; High mobility group proteins; High Mobility Group Proteins - biosynthesis; High Mobility Group Proteins - physiology; Humans; JunB protein; Leukemia; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Ligands; Medical sciences; Myc protein; Myeloid cells; Proteins; PU.1 protein; Repressor Proteins - biosynthesis; Repressor Proteins - physiology; RNA, Messenger - biosynthesis; Runx1 protein; Synergism; Transcription factors; Transcription Factors - physiology; Tumor Cells, Cultured; Tumor suppressor genes; Tumors; Up-Regulation; Atlanta Georgia; United States > US; Hematology; Growth; Leukemia; Gene overexpression; Malignant hemopathy; Cell differentiation; Myeloid cell
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403918

HMG-box containing protein 1 (HBP1) is a member of the high mobility group (HMG) of chromosomal proteins. Since HBP1 exhibits tumor-suppressor activity in nonmyeloid tissues, we examined the effects of ectopic overexpression of HBP1 upon the growth and differentiation of myeloid cells. We prepared transient and stable transfectants of the myeloblast cell line K562, which overexpress HBP1 mRNA and protein. HBP1 transfectants displayed slower growth in cell culture and reduced colony formation in soft agar, retardation of S-phase progression, reduced expression of cyclin D1 and D3 mRNAs and increased expression of p21 mRNA. HBP1 transfectants also underwent increased apoptosis, as demonstrated by morphology and binding of Annexin V. Fas ligand mRNA levels were increased in HBP1 transfectants, suggesting involvement of the Fas/Fas ligand pathway. HBP1 overexpression enhanced differentiation of K562 cells towards erythroid and megakaryocyte lineages, as evidenced by increased hemoglobin and CD41a expression. Overexpression of HBP1 modulated mRNA levels for myeloid-specific transcription factors C/EBPalpha, c-Myb, c-Myc, and JunB, as well as lineage-specific transcription factors PU.1, GATA-1, and RUNX1. These findings suggest that in myeloid cells HBP1 may serve as a tumor suppressor and a general differentiation inducer and may synergize with chemical differentiating agents to enhance lineage-specific differentiation.