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- W2172034404 abstract "Oncogenic forms of the small GTPase Ras increase the resistance of cells to killing by ionizing radiation (IR). Although not all of the signaling pathways for radioresistance are well defined, it is now clear that Ras-dependent signaling pathways involved in radioresistance include those mediated by phosphatidylinositol 3'-kinase (PI3-K) and Raf. Nevertheless, PI3-K and Raf together are not sufficient to reconstitute all of the resistance conferred by Ras, indicating that other effectors must also contribute. We show here that Ras-driven autocrine signaling through the epidermal growth factor receptor (EGFR) also contributes to radioresistance in Ras-transformed cells. Conditioned media (CM) collected from RIE-1 rat intestinal epithelial cells expressing oncogenic Ras increased the survival of irradiated cells. Ras-CM contains elevated levels of the EGFR ligand transforming growth factor alpha (TGF-alpha). Both Ras-CM and TGF-alpha stimulated EGFR phosphorylation, and exogenous TGF-alpha mimicked the effects of Ras-CM to increase radioresistance. Blocking EGFR signaling with the EGFR/HER-2 kinase inhibitor (KI) GW572016 decreased the postradiation survival of irradiated Ras-transformed cells and normal cells but had no effect on the survival of unirradiated cells. Ras-CM and TGF-alpha also increase PI3-K activity downstream of the EGFR and increase postradiation survival, both of which are abrogated by GW572016. Thus, Ras utilizes autocrine signaling through EGFR to increase radioresistance, and the EGFR KI GW572016 acts as a radiosensitizer. The observation that Ras-transformed cells can be sensitized to killing by ionizing radiation with GW572016 demonstrates that EGFR KIs could potentially be used to radiosensitize tumors in which radioresistance is dependent on Ras-driven autocrine signaling through EGFR." @default.
- W2172034404 created "2016-06-24" @default.
- W2172034404 creator A5004598334 @default.
- W2172034404 creator A5024561763 @default.
- W2172034404 creator A5062804155 @default.
- W2172034404 date "2003-11-15" @default.
- W2172034404 modified "2023-10-17" @default.
- W2172034404 title "Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance." @default.
- W2172034404 cites W1215185447 @default.
- W2172034404 cites W1491647197 @default.
- W2172034404 cites W1500815560 @default.
- W2172034404 cites W1506218460 @default.
- W2172034404 cites W1528312397 @default.
- W2172034404 cites W1550092936 @default.
- W2172034404 cites W166287817 @default.
- W2172034404 cites W1670810514 @default.
- W2172034404 cites W1803364112 @default.
- W2172034404 cites W1838340609 @default.
- W2172034404 cites W1862594138 @default.
- W2172034404 cites W1865083834 @default.
- W2172034404 cites W1873788002 @default.
- W2172034404 cites W1966865102 @default.
- W2172034404 cites W1968389835 @default.
- W2172034404 cites W1970866978 @default.
- W2172034404 cites W1973557583 @default.
- W2172034404 cites W1976748749 @default.
- W2172034404 cites W1978465495 @default.
- W2172034404 cites W1982729445 @default.
- W2172034404 cites W1990287461 @default.
- W2172034404 cites W1995992733 @default.
- W2172034404 cites W1999441881 @default.
- W2172034404 cites W2001598945 @default.
- W2172034404 cites W2005204942 @default.
- W2172034404 cites W2007179773 @default.
- W2172034404 cites W2008562323 @default.
- W2172034404 cites W2010660480 @default.
- W2172034404 cites W2014134684 @default.
- W2172034404 cites W2014815147 @default.
- W2172034404 cites W2022039302 @default.
- W2172034404 cites W2022118747 @default.
- W2172034404 cites W2023243044 @default.
- W2172034404 cites W2033707974 @default.
- W2172034404 cites W2036363901 @default.
- W2172034404 cites W2039231974 @default.
- W2172034404 cites W2043578693 @default.
- W2172034404 cites W2044416896 @default.
- W2172034404 cites W2060619750 @default.
- W2172034404 cites W2063960509 @default.
- W2172034404 cites W2066826805 @default.
- W2172034404 cites W2070075260 @default.
- W2172034404 cites W2071387709 @default.
- W2172034404 cites W2073423744 @default.
- W2172034404 cites W2075338210 @default.
- W2172034404 cites W2082130460 @default.
- W2172034404 cites W2084408056 @default.
- W2172034404 cites W2084769511 @default.
- W2172034404 cites W2098287668 @default.
- W2172034404 cites W2099234191 @default.
- W2172034404 cites W2100048123 @default.
- W2172034404 cites W2100669756 @default.
- W2172034404 cites W2103031848 @default.
- W2172034404 cites W2110866673 @default.
- W2172034404 cites W2112482436 @default.
- W2172034404 cites W2112825652 @default.
- W2172034404 cites W2114001916 @default.
- W2172034404 cites W2118364944 @default.
- W2172034404 cites W2125735022 @default.
- W2172034404 cites W2133453529 @default.
- W2172034404 cites W2135938911 @default.
- W2172034404 cites W2142093446 @default.
- W2172034404 cites W2142279958 @default.
- W2172034404 cites W2143536404 @default.
- W2172034404 cites W2147353530 @default.
- W2172034404 cites W2148685331 @default.
- W2172034404 cites W2154858152 @default.
- W2172034404 cites W2159227997 @default.
- W2172034404 cites W2159594827 @default.
- W2172034404 cites W2160796046 @default.
- W2172034404 cites W2161965319 @default.
- W2172034404 cites W2166655074 @default.
- W2172034404 cites W2166791970 @default.
- W2172034404 cites W2167003037 @default.
- W2172034404 cites W2168407724 @default.
- W2172034404 cites W2169547107 @default.
- W2172034404 cites W2173747422 @default.
- W2172034404 cites W2183542972 @default.
- W2172034404 cites W2260028313 @default.
- W2172034404 cites W2324578623 @default.
- W2172034404 cites W2330520802 @default.
- W2172034404 cites W2462795716 @default.
- W2172034404 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14633707" @default.
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