ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells

✍ Scribed by Audrey Fernandes; Anne W. Hamburger; Brenda I. Gerwin

• Book ID: 101235885
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 266 KB
• Volume: 83
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19991112)83:4<564::aid-ijc20>3.0.co;2-q

✦ Synopsis

Overexpression of the growth factor receptor ErbB-2/Her2/ Neu has been implicated in the development of non-small-cell lung cancer. We have reported that the transformation of human lung epithelial cells by c-erbB-2 also requires an active ErbB-1 (EGF receptor) and the autocrine production of its ligand, TGF-␣. In this report, we demonstrate that STAT 3 is constitutively activated in these cells by the TGF-␣-stimulated ErbB-1/-2 heterodimer complex. STAT 3 activation was confirmed by mobility shift assays and nuclear localization. ErbB-1 was required, but not sufficient for the TGF-␣induced activation of STATs. Inhibition of ErbB-2 kinase activity by tyrphostin AG825 prevented the constitutive activation of STAT 3 in the TGF-␣-producing, ErbB-1 expressing cell line. Our results demonstrate a requirement for ErbB-2 kinase activity to establish constitutive STAT 3 activation resulting from an autocrine ErbB-1/ TGF-␣ loop. Int.