Constitutively active Harvey Ras confers resistance to epidermal growth factor receptor-targeted therapy with cetuximab and gefitinib
Rodney B Luwor, Yang Lu, Xinqun Li, Ke Liang, Zhen Fan
Cancer Letters | ELSEVIER IRELAND LTD | Published : 2011
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..View full abstract
Awarded by US National Institutes of Health (NIH)
Awarded by US National Cancer Institute (NCI)
Awarded by NATIONAL CANCER INSTITUTE
This work was supported in part by a US National Institutes of Health (NIH) R01 award (CA129036 to Z.F.) and by the Cancer Center Support Grant CA016672 from US National Cancer Institute (NCI). We thank Bryan Tutt of the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for editorial assistance.