Localization of active, dually phosphorylated extracellular signal-regulated kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS mutations.

摘要: Summary Colorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate extracellular signal-regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis. However, immunohistochemical results on ERK activation in such tumors differ greatly. Recently, using a highly optimized method, we obtained evidence that high levels rectal adenocarcinomas were associated with resistance to radiochemotherapy. In order determine whether and/or correlate immunohistochemically detectable increases phosphorylation (pERK), stained biopsies from 36 CRC patients gene ( V600E: m ), (KRAS ) neither (BRAF/KRAS n this method. Staining was scored blind-coded specimens by two observers. stromal cells used as positive control. did not higher staining scores than BRAF/KRAS tumors. Although BRAFV600E occurred over 90% cancer all 9 tumors, 3 only showed for pERK less 10% nuclei. The same applied 4 14 A phophorylation-insensitive antibody demonstrated lack reflect defect expression ERK1/2 protein. Thus, increased does even procedure. Further studies are required reflects differences counterregulatory molecules, including phosphatases.