| Popis: |
The hypothesis that ethanolamine deficiency alters the membrane phospholipid composition to such an extent that transduction of growth factor signals is inhibited was examined in two ethanolamine-responsive normal human cell lines, epidermal keratinocytes and mammary epithelial cells. Incubation of keratinocytes and human mammary epithelial cells in media without ethanolamine resulted in a 55.2% and 53.1% reduction in cell proliferation respectively. Further studies with mammary epithelial cells showed that in the absence of ethanolamine in the growth medium, incorporation of ($\sp3$H) -thymidine into DNA was reduced by 5-fold. In keratinocytes, ethanolamine significantly enhanced the stimulatory effects of insulin and epidermal growth factor on DNA synthesis by 69% and 40.5% respectively. Insulin, in particular, was critical for the optimal proliferation of keratinocytes. Addition of ethanolamine to the growth media of mammary epithelial cells enabled a normal progression of cells through the cell cycle. In contrast, ethanolamine-deficient cells accumulated in the G0/G1 phase of the cell cycle. Ethanolamine but not dimethylethanolamine or monomethylethanolamine was mitogenic for quiescent ethanolamine-deficient cells. Proliferation of cells incubated in dimethylethanolamine and monomethylethanolamine was 55.5% and 47.2%, respectively, of cells incubated in ethanolamine-sufficient media. The incorporation of ($\sp3$H) -glycerol into phosphatidylethanolamine in ethanolamine-deficient keratinocytes and mammary epithelial cells was significantly reduced by 58.5% and 64.3%, respectively, compared to controls. The incorporation of ($\sp3$H) -glycerol into other glycerophospholipids in ethanolamine-sufficient and ethanolamine-deficient cells were unchanged. Insulin stimulation of quiescent keratinocytes and mammary epithelial cells in the presence of ethanolamine activated mitogen-activated protein kinase. (Abstract shortened by UMI.) |
