Lang, Sven A. and Hackl, Christina and Moser, Christian and Fichtner-Feigl, Stefan and Koehl, Gudrun E. and Schlitt, Hans J. and Geissler, Edward K. and Stoeltzing, Oliver (2010) Implication of RICTOR in the mTOR inhibitor-mediated induction of insulin-like growth factor-I receptor (IGF-IR) and human epidermal growth factor receptor-2 (Her2) expression in gastrointestinal cancer cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1803 (4). pp. 435-442. ISSN 0167-4889,
Full text not available from this repository. (Request a copy)Abstract
Inhibition of mTORC1 with the mTOR inhibitor rapamycin may lead to an induction of Akt phosphorylation in cancer cells via mTORC2 activation. Using gastric and pancreatic cancer cells, we further investigated this paradoxical signaling response and found that rapamycin additionally up-regulates both IGF-IR and Her2 expression. Using RNAi for down-regulating RICTOR, this induction of receptor kinase expression was identified to be mediated via an mTORC2-induced Akt activation. Moreover, mTORC2 inhibition reduced the phosphorylation of GSK-3 and NF-kappa B, and significantly impaired cancer cell motility. In conclusion, inhibition of mTORC2 may abrogate unfavorable signaling effects of mTOR inhibitors, hence providing a novel rationale for therapy. (C) 2010 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN PANCREATIC-CANCER; PLASMINOGEN-ACTIVATOR RECEPTOR; ORTHOTOPIC TUMOR-GROWTH; GASTRIC-CANCER; MAMMALIAN TARGET; AUTOCRINE LOOP; C-MET; RAPAMYCIN; AKT; THERAPY; IGF-IR; mTOR; RICTOR; Gastrointestinal cancer; Her2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 07:53 |
| Last Modified: | 03 Aug 2020 07:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24855 |
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