| | Category | BI | L06 | The Effects of Epidermal Growth Factor (EGF)-like Growth Factor |
| | Ligands on EGF |
| | Abstract | Epidermal growth factor receptor (EGFR) is often found to be over |
| | expressed in various cancers resulting in accumulation of EGFR to the |
| | plasma membranes of malignant epithelial tumors. Previous research has |
| | shown that one of the seven EGFR ligands, amphiregulin (AREG), |
| | promotes EGFR recycling to the plasma membrane over receptor |
| | internalization and degradation as observed following “canonical” EGF |
| | stimulation of EGFR. In this study, we used six different EGF-like ligands to |
| | investigate their effects on modulating cell growth and EGFR localization in |
| | SUM-149 cells expressing AREG short hairpin RNA (shRNA), or knock- |
| | down cells, in which AREG expression is muted. By western blot analysis, |
| | growth assays, and immunofluorescent staining assays, it was found |
| | that high concentrations of EGF promoted internalization of membrane- |
| | localized EGFR and stunted cell growth. On the contrary, low |
| | concentrations of EGF allowed for membrane-localized EGFR to remain on |
| | the cell surface and enhanced cell proliferation in the AREG knock-down |
| | cells. These results suggest that AREG expression and EGFR membrane |
| | accumulation are independent factors. Furthermore, the results of the |
| | immunofluorescence assays showed that SUM-149 cells, which express |
| | endogenous AREG, and SUM-149 AREG knock-downs had similar levels |
| | of EGFR plasma membrane accumulation. However, a morphological |
| | difference in the manner of invasion of the SUM-149 cells and the SUM- |
| | 149 AREG knock-down cells was observed. SUM-149 cells, expressing |
| | endogenous AREG, migrated in sheets while the knock-down cells were |
| | more separate and spread out while migrating. These results further |
| | suggest that AREG expression facilitates cancer cell invasion, as indicated |
| | by the cancer cells’ movement in sheets. If this is so, AREG could be used |
| | as a potential biomarker, allowing for specific chemotherapeutic |
| | strategies. |
| | Bibliography | 1) Mendelsohn, Baird, Fan, Markowitz. “Growth Factors and their |
| | Receptors in Epithelial |
| | Malignancies.” Cancer Biology. 2001 2) McBryan, Howlin, Napoletano, |
| | Martin. “Amphiregulin: Role in Mammary Gland Development |
| | and Breast Cancer.” Journal of Mammary Gland Biology and Neoplasia 13 |
| | (2008): 159-169. 3) Wilmarth, Baillo, Dzubinski, Wilson, Riese, Ethier. |
| | “Altered EGFR Localization and |
| | Degradation in Human Breast Cancer Cells with an Amphiregulin/EGFR |
| | Autocrine Loop.” Cell |
| | Signal 21 (2009): 212-219. |