| Autor: |
Zorbas, Mark A., Yeoman, Lynn C. |
| Zdroj: |
Experimental Cell Research; May 1993, Vol. 206 Issue: 1 p49-57, 9p |
| Abstrakt: |
Transforming growth factor-α (TGFα) is able to elicit growth in many target cells expressing a functional epidermal growth factor (EGF) receptor. Other laboratories have reported that the TGFα precursor polypeptide (proTGFα) is inefficiently cleaved from many target cells, resulting in accumulation of proTGFα on the cell surface. Since it has been shown that noncleavable, mutated cell-associated TGFα can stimulate cell growth on receptor-bearing adjacent cells, we have tried to determine whether cell-associated TGFα populations might be involved in supporting autonomous cell growth regulatory mechanisms in a human colon carcinoma cell line, HCT116. To address this question, the levels of secreted and nonsecreted TGFα produced were determined. Cells grown to medium cell density (40-60% confluent) expressed the greatest percentage of cell-associated TGFα (50%). Incubation of HCT116 cells with 0.1 U/ml porcine pancreatic elastase resulted in the release of 67% of the cell-associated TGFα into their medium and caused the treated cells to acquire a newly established growth sensitivity to exogenous TGFα at a ligand concentration of 1.0 nM. Western blot analysis of EGF receptor phosphotyrosine levels showed a decrease in phosphotyrosine content after elastase treatment. Phosphotyrosine content was restored to basal levels if elastase treatment was followed by addition of exogenous TGFα or EGF. These results suggest that HCT116 cells use a "closed" autocrine loop between cell-associated TGFα species and their EGF receptor to stimulate their cell growth. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
