Mori, Akira and Moser, Christian and Lang, Sven A. and Hackl, Christina and Gottfried, Eva and Kreutz, Marina and Schlitt, Hans J. and Geissler, Edward K. and Stoeltzing, Oliver (2009) Up-Regulation of Kruppel-Like Factor 5 in Pancreatic Cancer Is Promoted by Interleukin-1 beta Signaling and Hypoxia-Inducible Factor-1 alpha. MOLECULAR CANCER RESEARCH, 7 (8). pp. 1390-1398. ISSN 1541-7786, 1557-3125
Full text not available from this repository. (Request a copy)Abstract
Kruppel-like factor 5 (KLF5) is a transcription factor involved in cell transformation, proliferation, and carcinogenesis that can be up-regulated by RAS mutations. However, controversy persists as to whether it functions as a tumor suppressor or as an oncogene. Because KRAS is frequently mutated in pancreatic cancer, we investigated the regulation of KLF5 in this cancer entity. Our results show that KLF5 is overexpressed in pancreatic cancer cells and exceeds KLF5 expression of KRAS-mutated colon cancer cells. Surprisingly, inhibition of B-Raf/C-Raf or MAPK/Erk did not reduce KLF5 levels, suggesting that KLF5 expression is not promoted by KRAS-Raf-MEK-Erk signaling in pancreatic cancer. This finding is in striking contrast to reports on MEK-Erk-mediated KLF5 induction in colon cancer cells. Moreover, KLF5 expression levels neither correlated with the mutational status of KRAS nor with MEK phosphorylation in pancreatic cancer cells. Importantly, KLF5 was significantly up-regulated by interleukin (IL)-1 beta or hypoxia. The IL-1 beta-medlated induction of KLF5 was diminished by blocking the p38 pathway. In addition, blocking IL-1R reduced the constitutive KLF5 expression, suggesting an autocrine activation loop. Moreover, KLF5 coimmunoprecipitated with hypoxia-inducible factor-la (HIF-1 alpha) and HIF-1 alpha(siRNA) reduced constitutive KLF5. Similarly, KLF5(siRNA) reduced the expression of the HIF-1a target gene GLUT-1. Furthermore, KLF5 expression was significantly elevated by high cell density, by anchorage-independent cell growth, and in tumor spheroids. Down-regulation of KLF5 by RNA! reduced the expression of
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; HUMAN COLON-CANCER; FACTOR-I; CELL-LINES; FACTOR EXPRESSION; CARCINOMA CELLS; AUTOCRINE LOOP; FACTOR 1-ALPHA; BREAST-CANCER; K-RAS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 08:13 |
| Last Modified: | 10 Sep 2020 08:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28656 |
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