title: Aberrant intracellular IGF-1R beta-subunit makes receptor knockout cells (IGF1R-/-) susceptible to oncogenic transformation.
abstract: Insulin-like growth factor 1 receptor (IGF-1R) is important for transformation of cells with cellular and viral oncogenes. This knowledge is mainly based on experiments on IGF-1R knockout mouse fibroblasts, which mostly are unable to transform after introduction of various oncogenes. Recently, we observed two variants of R- cells, one of which (R-s) surprisingly expresses the beta-subunit of IGF-1R whereas the other one (R-r) does not. Here we show that the beta-subunit is localized intracellularly and forms perinuclear aggregates. It expresses tyrosine kinase activity and appears to be crucial for cell survival since knockdown of it kills the R-s cells. H-RasV12 and/or polyoma middle T-antigen fail to transform R-r, whereas R- cells expressing the beta-subunit were transformed as assessed by formation of colonies in soft agar. The oncogenic transformation of R-s cells was, however, abrogated when the aberrant beta-subunit was knockdown by siRNA. The occurrence of intracellular IGF-1R, especially in tumor cells, has been widely reported but its function has not been understood. Our study provides evidence that it may be important for cell survival and transformation.
authors.affiliation: Department of Oncology and Pathology, CCK R8:04, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Natalishvili
authors.forename: Magnus
authors.initials: M
authors.lastname: Axelson
authors.forename: Leonard
authors.initials: L
authors.lastname: Girnita
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
authors.forename: Daiana
authors.initials: D
authors.lastname: Vasilcanu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005453:Fluorescence; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases