| First Author | Natalishvili N | Year | 2009 |
| Journal | Exp Cell Res | Volume | 315 |
| Issue | 8 | Pages | 1458-67 |
| PubMed ID | 19302825 | Mgi Jnum | J:338067 |
| Mgi Id | MGI:7510062 | Doi | 10.1016/j.yexcr.2009.01.008 |
| Citation | Natalishvili N, et al. (2009) Aberrant intracellular IGF-1R beta-subunit makes receptor knockout cells (IGF1R-/-) susceptible to oncogenic transformation. Exp Cell Res 315(8):1458-67 |
| abstractText | 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. |
