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Resistance to Selumetinib (AZD6244) in Colorectal Cancer Cell Lines is Mediated by p70S6K and RPS6 Activation^1^ by Silvina Grasso; Elena Tristante; Miguel Saceda; Pablo Carbonell; Leticia Mayor-López; Mar Carballo-Santana; Estefanía Carrasco-García; Lourdes Rocamora-Reverte; Pilar García-Morales; Fernando Carballo; José A. Ferragut; Isabel Martínez-Lacaci is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Resistance to Selumetinib (AZD6244) in Colorectal Cancer Cell Lines is Mediated by p70S6K and RPS6 Activation^1^ about?
Selumetinib (AZD6244, ARRY-142886) is a MEK1/2 inhibitor that has gained interest as an anti-tumour agent. We have determined the degree of sensitivity/resistance to Selumetinib in a panel of colorectal cancer cell lines using cell proliferation and soft agar assays. Sensitive cell lines underwent G~1~ arrest, whereas Selumetinib had no effect on the cell cycle of resistant cells. Some of the resistant cell lines showed high levels of ERK1/2 phosphorylation in the absence of serum. Selumetinib inhibited phosphorylation of ERK1/2 and RSK and had no effect on AKT phosphorylation in both sensitive and resistant cells. Furthermore, mutations in __KRAS, BRAF,__ or __PIK3CA__ were not clearly associated with Selumetinib resistance. Surprisingly, Selumetinib was able to inhibit phosphorylation of p70 S6 kinase (p70S6K) and its downstream target ribosomal protein S6 (RPS6) in sensitive cell lines. However, p70S6K and RPS6 phosphorylation remained unaffected or even increased in resistant cells. Moreover, in some of the resistant cell lines p70S6K and RPS6 were phosphorylated in the absence of serum. Interestingly, colorectal primary cultures derived from tumours excised to patients exhibit
Who reads Resistance to Selumetinib (AZD6244) in Colorectal Cancer Cell Lines is Mediated by p70S6K and RPS6 Activation^1^?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Silvina Grasso; Elena Tristante; Miguel Saceda; Pablo Carbonell; Leticia Mayor-López; Mar Carballo-Santana; Estefanía Carrasco-García; Lourdes Rocamora-Reverte; Pilar García-Morales; Fernando Carballo; José A. Ferragut; Isabel Martínez-Lacaci
- Publisher
- Neoplasia Press; Elsevier ; Elsevier BV; Basingstoke: Nature Publishing Group (ISSN 1522-8002)
- Published
- 2014
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)