کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2113761 | 1084492 | 2011 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Constitutively active Harvey Ras confers resistance to epidermal growth factor receptor–targeted therapy with cetuximab and gefitinib Constitutively active Harvey Ras confers resistance to epidermal growth factor receptor–targeted therapy with cetuximab and gefitinib](/preview/png/2113761.png)
Kirsten Ras (K-Ras) mutations have been implicated as a key predictive marker of resistance to therapies targeting the epidermal growth factor receptor (EGFR). To determine whether Harvey Ras (H-Ras) mutations also can confer resistance to EGFR-targeted therapy, we expressed a constitutively active H-Ras (Ras G12V) in A431 human vulvar squamous carcinoma cells. Compared with corresponding control cells, A431-Ras cells exhibited marked resistance to the EGFR inhibitors cetuximab and gefitinib, reducing inhibition of Akt and Erk phosphorylation, inhibition of HIF-1α expression and transcriptional activity, and antitumor effects in vitro and in vivo. Our data indicate that constitutively active H-Ras can also confer resistance to anti-EGFR therapy in cancer cells.
Journal: Cancer Letters - Volume 306, Issue 1, 1 July 2011, Pages 85–91