Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lineage and state of differentiation of cells in the mammalian haemopoietic compartment is associated with specific patterns of homeobox gene expression (EMBO J. 7, 2131, 1988). Agents which influence homeobox gene expression are thus of great interest in the study of human leukemias. Retinoic acid has direct regulatory actions on homeobox gene transcription (TIBS 158, 52, 1989; Differentiation 37, 773, 1988) and can induce select human leukemia cell lines to undergo terminal differentiation in vitro (Proc. natl Acad. Sci. U.S.A. 77, 2936, 1980). Retinoic acid is also a known teratogen for vertebrate foetal limb-bud development. Some of the teratogenic effects are duplicated by the drug Thalidomide (Embryopathic Activity of Drugs, Little Brown, Boston, p. 167, 1965; Haematological Cytology, Wolf Med. Pub. Ltd, London, p. 118, 1982). To investigate Thalidomide for other retinoid-like effects, we exposed cultures of human leukemia K562 cells to the metabolites generated in a Thalidomide hepatic-microsomal enzyme drug metabolizing system (Proc. natl Acad. Sci. U.S.A. 78, 2545, 1981). Here we report evidence that a single 2 h pulse-exposure to Thalidomide metabolites, induces K562 cells to undergo morphological differentiation in vitro. We also demonstrate a significant cytotoxic effect for these metabolites.
 ...
PMID:Induction of morphological differentiation in the human leukemic cell line K562 by exposure to thalidomide metabolites. 201 4

Msx-1 and Msx-2 are two closely related homeobox genes expressed in cephalic neural crest tooth buds, the optic cup endocardial cushions, and the developing limb [Hill and Davidson, 1991; Monaghan et al., 1991; Robert et al., 1991]. These sites correspond to regions of active cell segregation and proliferation under the influence of epithelial-mesenchymal cell interactions [Brown et al., 1993; Davidson et al., 1991], suggesting that Msx-1 and Msx-2 regulate cell-cell interactions. We have investigated the potential relationship between expression of the Msh homeobox genes (Msx-1 and Msx-2) and cadherin-mediated cell adhesion and cell sorting. We report that cell lines stably expressing Msx-1 or Msx-2 differentially sort on the basis of Msh gene expression. We demonstrate in vitro that initial cell aggregation involves calcium-dependent adhesion molecules (cadherins) and that Msh genes regulate cadherin-mediated adhesion. These results support the hypothesis that Msh genes play a role in the regulation of cell-cell adhesion and provide a link between the genetic phenomena of homeobox gene expression and cellular events involved in morphogenesis, including cell sorting and proliferation.
 ...
PMID:Msh homeobox genes regulate cadherin-mediated cell adhesion and cell-cell sorting. 963 4