ABSTRACT
A C6 beta-chemokine, CKbeta8-1, suppressed the colony formation of CD34 + cells of human cord blood (CB). Molecular mechanisms involved in CKbeta8-1-medicated suppression of colony formation of CD34 + cells are not known. To address this issue, the level of various G1/S cell cycle regulating proteins in CKbeta8-1-treated CD34 + cells were compared with those in untreated CD34 + cells. CKbeta8-1 did not significantly alter the expression of the G1/S cycle regulation proteins (cyclin D1, D3, and E), CDK inhibitor (p27and Rb), and other cell proliferation regulation protein (p53) in CB CD34 + cells. Here we describe an in vitro system in which CB CD34 + cells were committed to a multipotent progenitor lineage of colony forming units-granulocyte/macrophage (CFU-GM) by a simple combination of recombinant human (rh) GM-CSF and rhIL-3. In this culture system, we found that cyclin E protein appeared later and disappeared faster in the CKbeta8-1-treated cells than in the control cells during CFU-GM lineage development. These findings suggested that cyclin E may play a role in suppressing the colony formation of CFU-GM by CKbeta8-1.
Subject(s)
Humans , Antigens, CD34/metabolism , Cell Cycle Proteins/metabolism , Cell Lineage , Cells, Cultured , Chemokines, CC/pharmacology , Cyclin E/metabolism , Fetal Blood/cytology , G1 Phase/drug effects , Gene Expression Regulation/drug effects , Granulocytes/cytology , Growth Substances/pharmacology , Macrophages/cytology , Stem Cells/cytologyABSTRACT
Cyclins are the regulatory subunits of cyclin-dependent kinase and play an important role in cell proliferation. Many tumors, such as colon, breast and gastric carcinomas are known to be involved in the deregulation or amplification of cyclins, especially cyclin E, which involves the restriction point of G1-S transition. We investigated the expression of cyclin E in benign and malignant epithelial tumors of the gallbladder and compared the results with the activity of cell proliferation by the Ki67 antigen using immunohistochemical staining. Cyclin E was expressed in the adenocarcinoma tissue in 33.3% of patients (4 out of 12 cases), whereas only one out of 8 cases of adenoma expressed cyclin E (12.5%). There was a correlation between cyclin E expression and the Ki67 labeling index. These results suggest that the high expression of cyclin E in adenocarcinoma of the gallbladder is related to a high rate of cell proliferation.