Biomaterial Database

Wilms' tumor gene, WT1, mRNA is down-regulated during induction of erythroid and megakaryocytic differentiation of K562 cells. 1994

S A Phelan, and C Lindberg, and K M Call

Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.

Evidence implicates the product of the Wilms' tumor suppressor gene, WT1, in proliferation and differentiation of target tissues during development. Study of the regulation of other tumor suppressor genes during these processes has been instrumental in defining their interactions and functions. In this study, we performed experiments to assess the suitability of the human K562 erythroleukemia cell line for studying the WT1 gene during differentiation. We predicted that WT1 mRNA would be decreased during induction of differentiation of K562 cells based on observations of decreased WT1 mRNA during kidney development and in differentiated Wilms' tumors and leukemias. Accordingly, we found that WT1 mRNA was down-regulated in K562 cells during induction of erythroid and megakaryocytic differentiation by sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate, respectively. Down-regulation of WT1 mRNA was not a generalized phenomenon of growth inhibition. WT1 mRNA was not down-regulated when 12-O-tetradecanoylphorbol-13-acetate-induced differentiation was blocked by bryostatin-1. During 12-O-tetradecanoylphorbol-13-acetate treatment, the decrease in WT1 mRNA was rapid (within 5 min), continuous, and occurred, at least in part, posttranscriptionally. An analysis of the 5' flanking region and transcription initiation sites of the human WT1 gene also was performed. Our data suggest that K562 cells will be a valuable system for unraveling signal transduction pathways by which WT1 is regulated and for investigating the interactions and role of WT1 in differentiation.

UI	MeSH Term	Description	Entries
D007783	Lactones	Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.	Lactone
D007938	Leukemia	A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)	Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D008533	Megakaryocytes	Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.	Megakaryocyte
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002461	Cell Line, Transformed	Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.	Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000943	Antigens, Differentiation	Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.	Differentiation Antigen,Differentiation Antigens,Differentiation Antigens, Hairy Cell Leukemia,Differentiation Marker,Differentiation Markers,Leu Antigen,Leu Antigens,Marker Antigen,Marker Antigens,Markers, Differentiation,Antigen, Differentiation,Antigen, Leu,Antigen, Marker,Antigens, Leu,Antigens, Marker,Marker, Differentiation