STAT3 mediates the survival signal in oncogenic ras‐transfected intestinal epithelial cells

• Published in: International journal of cancer Vol. 78; no. 3; pp. 326 - 330
• Main Authors: Zushi, Shinichiro, Shinomura, Yasuhisa, Kiyohara, Tatsuya, Miyazaki, Yoshiji, Kondo, Shinya, Sugimachi, Masamitsu, Higashimoto, Yoshifumi, Kanayama, Shuji, Matsuzawa, Yuji
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 29-10-1998; Wiley-Liss
• Subjects: Acute-Phase Proteins - metabolism; Animals; bcl-X Protein; Biological and medical sciences; Cell Line; Cell physiology; Cell Survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; DNA Fragmentation; DNA-Binding Proteins - metabolism; Enzyme Inhibitors - pharmacology; Epidermal Growth Factor - pharmacology; Epidermal Growth Factor - physiology; Fundamental and applied biological sciences. Psychology; Genes, ras; Intestinal Mucosa - cytology; Intestinal Mucosa - physiology; Molecular and cellular biology; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Quinazolines; Rats; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators - metabolism; Transfection; Tyrphostins - pharmacology; Rat; Rodentia; Gut; Resistance; Signal transduction; Vertebrata; Regulation(control); Mammalia; Transfection; Cell death; Animal; C-Onc gene; Established cell line; Transcription factor STAT3; Epithelial cell; Protooncogene; Apoptosis
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19981029)78:3<326::AID-IJC12>3.0.CO;2-4

The oncogenic ras mutation is a common and critical step in gastrointestinal carcinogenesis. In a previous study, we demonstrated that oncogenic ras activated the EGF‐related peptide autocrine loop and that the apoptosis resistance observed in the oncogenic ras‐stimulated cell (IEC‐ras cell) was dependent on this activated EGF‐related peptide autocrine loop. STATs (signal transducers and activators of transcription), first identified as intracellular signal transducers stimulated by cytokines, are known to also be activated by EGF. However, the role of STATs in the survival signal of IEC‐ras cells is not clear. In the present study, we demonstrate that STAT3 is constitutively activated in ras‐stimulated cells and that STAT3 activation is considerably suppressed by the EGF‐specific receptor kinase inhibitor AG1478. We also show that disruption of the STAT3 pathway by introduction of a dominant‐negative STAT3 mutant abolishes the apoptosis resistance against UVC and MMC treatment observed in IEC‐ras cells without affecting proliferation. Moreover, the expression of Bcl‐2 and Bcl‐xL, apoptosis‐suppressive proteins, is reduced in dominant‐negative STAT3‐transfected cells. Thus, STAT3 appears to be an important mediator of the anti‐apoptotic signal in IEC‐ras cells. Int. J. Cancer 78:326–330, 1998.© 1998 Wiley‐Liss, Inc.