Premium
STAT3 mediates the survival signal in oncogenic ras ‐transfected intestinal epithelial cells
Author(s) -
Zushi Shinichiro,
Shinomura Yasuhisa,
Kiyohara Tatsuya,
Miyazaki Yoshiji,
Kondo Shinya,
Sugimachi Masamitsu,
Higashimoto Yoshifumi,
Kanayama Shuji,
Matsuzawa Yuji
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981029)78:3<326::aid-ijc12>3.0.co;2-4
Subject(s) - autocrine signalling , stat3 , transfection , biology , signal transduction , apoptosis , cancer research , stat protein , microbiology and biotechnology , epidermal growth factor , receptor , cell culture , biochemistry , genetics
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.