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Interruption of NFκb–stat1 signaling mediates EGF‐induced cell‐cycle arrest
Author(s) -
Ohtsubo Masafumi,
Takayanagi Atsushi,
Gamou Shinobu,
Shimizu Nobuyoshi
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(200007)184:1<131::aid-jcp14>3.0.co;2-w
Subject(s) - a431 cells , microbiology and biotechnology , epidermal growth factor , biology , signal transduction , stat1 , cell growth , intracellular , cell cycle , effector , kinase , receptor , cell , biochemistry , oncogene
It is known that EGF induces the cell‐cycle arrest in A431 cells that possess high numbers of EGF receptors and it was previously suggested that p21/WAF1 protein was a major effector molecule of the EGF‐mediated cell‐cycle arrest of A431 cells. Here, we further investigate this phenomenon using the decoy double‐strand oligonucleotides for STAT‐binding sequence (STAT decoy) and IκB, an inhibitor of the nuclear factor kappa B (NFκB). Addition of STAT decoy restored EGF‐induced A431 cell‐growth arrest. Interestingly, infection of adenovirus vectors to express IκB (AxIκBαΔN) as the inhibitor of NFκB also reversed the A431 cell‐growth inhibition. The individual treatment of two inhibitors partially inhibited the WAF1 gene expression, whereas simultaneous treatment of two inhibitors exhibited more efficient inhibition. These observations suggest the activation of NFκB via IκB degradation and STAT1 via specific receptor kinase activity synergistically induce WAF1 gene expression in A431 cells. Thus, NFκB and STAT1 pathways mutually interact to play an important role in the EGF‐induced intracellular reaction. J. Cell. Physiol. 184:131–137, 2000. © 2000 Wiley‐Liss, Inc.