The Effect Of Forced Expression Of K-Ras Mutation On Gastrointestinal Cancer Cells And Igf-Ir Targeting Therapy

Background u0026 Aims: Mutation in k-ras plays important roles in both the progression and the resistance for anti-EGFR therapy in gastrointestinal tumors. Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of many tumors. We have previously shown successful therapy for gastrointestinal cancer cell lines with k-ras mutation using recombinant adenoviruses expressing dominant negative IGF-IR (IGF-IR/dn) and an anti-IGF-IR monoclonal antibody. In this study, we sought to evaluate the effect of k-ras mutation on gastrointestinal cancer cell lines and IGF-IR targeting therapies for those cells. Methods: We made stable transfectants of mutated k-ras in gastrointestinal cancer cell lines. We assessed the effect of forced expression of mutated k-ras on proliferartion, apoptosis induction, migration, and invasion in gastrointestinal cancer cell lines. Then we assessed the anti-tumor effect of IGF-IR/dn on mutated k-ras transfctomas. Results: Overexpression of mutated k-ras let gastrointestinal cancer cell lines be more agrressive phenotypes, such as more proliferative, more anti-apoptotic, more movable, and more invasive. IGF-IR/dn inhibited cell growth, colony formation, migration, and invasion, but induceed apoptosis of gastrointestinal cancer cells with or without mutated k-ras expression. Conclusions: K-ras mutation might be inportant for progressive phonotype in gastrointestinal cancers. IGF-IR might be a good molecular therapeutic target for gastrointestinal cancers even if k-ras is mutated. Citation Format: Yasushi Adachi, Yasutaka Matsunaga, Yasushi Sasaki, Katsuhiko Nosho, Hiroyuki Yamamoto, Yoshiaki Arimura, Takao Endo, Yasuo Kato, Takashi Tokino, David P. Carbone, Yasuhisa Shinomura. The effect of forced expression of k-ras mutation on gastrointestinal cancer cells and IGF-IR targeting therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3474. doi:10.1158/1538-7445.AM2015-3474