| Autor: |
Chan JK; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford Cancer Center, 300 Pasteur Drive HH333, Stanford, CA 94305-5317, USA. johnchan@stanford.edu, Pham H, You XJ, Cloven NG, Burger RA, Rose GS, Van Nostrand K, Korc M, Disaia PJ, Fan H |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer research [Cancer Res] 2005 Apr 15; Vol. 65 (8), pp. 3243-8. |
| DOI: |
10.1158/0008-5472.CAN-03-3013 |
| Abstrakt: |
The overexpression of the epidermal growth factor receptor (EGFR) is associated with a poor prognosis in ovarian cancer. The dominant-negative EGFR (EGFR-DNR) is a truncated receptor that lacks the tyrosine kinase domain and is devoid of signaling capability. This study tested the effects of a EGFR-DNR approach in ovarian cancer cells. NuTu-19, a rat ovarian cancer cell line was rendered resistant to cisplatin. Both NuTu-19 and resistant cells were infected with a retroviral vector containing the EGFR-DNR. NuTu-19 and NuTu-DNR (NuTu-19 cells expressing the EGFR-DNR) were injected into Fisher 344 immunocompetent rats. Western blot analyses were used to assess signal transduction pathways. All rats injected with NuTu-DNR cells remained healthy following tumor injection. In contrast, 100% of the rats injected with the NuTu-19 and NuTu-Sham (NuTu-19 cells expressing an empty vector) died of disease progression at the end of 15 weeks (P = 0.00009). On Western blot analysis, both NuTu-19 and NuTu-Sham cells showed a strong activation of mitogen-activated protein kinase (MAPK) after exposure to EGF. Cisplatin-resistant cell lines showed an enhanced EGF stimulatory effect via the MAPK pathway compared with parental cells. The EGFR-DNR significantly reduced the ability of EGF to induce cell signaling through the MAPK pathway. Lastly, the EGFR-DNR can partially reverse cisplatin resistance in drug-resistant cells. The EGFR-DNR approach suggests that EGFR confers a growth advantage to NuTu-19 cells in vivo. Thus, EGFR blockade may ultimately prove to be a useful therapeutic tool in the treatment of cisplatin-sensitive and cisplatin-resistant ovarian cancers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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