| First Author | Lizama C | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1813 |
| Issue | 1 | Pages | 120-8 |
| PubMed ID | 20800622 | Mgi Jnum | J:170223 |
| Mgi Id | MGI:4944158 | Doi | 10.1016/j.bbamcr.2010.08.003 |
| Citation | Lizama C, et al. (2011) Etoposide induces apoptosis and upregulation of TACE/ADAM17 and ADAM10 in an in vitro male germ cell line model. Biochim Biophys Acta 1813(1):120-8 |
| abstractText | Etoposide is a widely used anticancer drug in the treatment of different tumors. Etoposide is known to activate a wide range of intracellular signals, which may in turn induce cellular responses other than apoptosis. ADAM10 and TACE/ADAM17 belong to a family of transmembrane extracellular metalloproteinases involved in paracrine/juxtacrine regulation of many signaling pathways. The aim of this work was to evaluate if etoposide induces upregulation of ADAM10 or TACE/ADAM17 in two cell lines (GC-1 and GC-2) derived from male germ cells. Results showed that etoposide induced apoptosis in a dose-response manner in both GC-1 and GC-2 cells. Apoptosis started to increase 6h after etoposide addition in GC-2 cells, whereas the same was observed 18h after addition to the GC-1 cells. Protein and mRNA levels of ADAM10 and TACE/ADAM17 increased 18h after etoposide was removed from the GC-1 cells. In GC-2 cells, the protein levels of both proteins increased 12h after etoposide was removed. ADAM10 mRNA increased after 3h and then steadily decreased up to 12h after removal, whereas TACE/ADAM17 mRNA decreased after etoposide removal. Finally, apoptosis was prevented in GC-1 and GC-2 cells by the addition of pharmacological inhibitors of ADAM10 and TACE/ADAM17 to the culture medium of etoposide-treated cells. Our results show for the first time that etoposide upregulates ADAM10 and TACE/ADAM17 mRNA and protein levels. In addition, we also show that ADAM10 and TACE/ADAM17 have a role in etoposide-induced apoptosis. |
