| Autor: |
Huang, Fei, Sauma, Samir, Yan, Zhongfa, Friedman, Eileen |
| Zdroj: |
Experimental Cell Research; July 1995, Vol. 219 Issue: 1 p8-14, 7p |
| Abstrakt: |
As colon epithelial cells migrate up the cylindrical colonic crypt, they terminally differentiate and lose their ability to divide. Elevated levels of the epithelial cell mitogen TGFα have been found at the top of the crypt by other investigators, causing us to speculate that colon epithelial cells lose mitogenic response to TGFα as they differentiate. We tested this hypothesis by using the HT29 colon carcinoma sublines U4 and U4H as models of one colonocyte lineage, fluid-transporting enterocytes. TGFα was mitogenic for the U4 cells, but inhibited the growth of the more differentiated U4H cells. However, p44 MAP kinase was activated by TGFα in both U4 and U4H cells, as well as in two control undifferentiated HT29 sublines which showed no change in proliferation in response to TGFα. In addition, TGFα activated the EGF receptor in each line by increasing its tyrosine phosphorylation. No relationship was found in these four lines between response to TGFα and level of expression of either the EGF receptor or two EGF receptor ligands, TGFα and amphiregulin. Activated EGF receptors initiate both growth-inhibitory and mitogenic signals in these cells since blocking some of the EGF receptors on TGFα-growth-inhibited U4H cells and TGFα-unresponsive U9 cells overrode the inhibitory signals and made both U9 and U4H cells sensitive to mitogenesis by added TGFα. These data imply that upon reaching stages of greater maturation, colon enterocytes lose proliferative response to TGFα because of changes in signaling by their EGF receptors. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full Text from ScienceDirect