Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation

Citation
Rg. Watts et al., Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation, ONCOGENE, 17(26), 1998, pp. 3493-3498
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
17
Issue
26
Year of publication
1998
Pages
3493 - 3498
Database
ISI
SICI code
0950-9232(199812)17:26<3493:EODNEI>2.0.ZU;2-L
Abstract
The mitogen activated protein (MAP) kinases or extracellular signal-regulat ed kinases (Erks) are activated in response to Ras expression or exposure t o tumor promoters or to growth factors, and have been implicated in AP-I tr ansactivation in some models. We have shown that tumor promoter induced act ivation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model. Jun and Fos family protein le vels have been found not to be limiting for AP-l response. The present stud y asks whether activation of Erks1 and 2 is required for AP-1 transactivati on and transformation of JB6 cells and whether Erks might be targeted for c ancer prevention. Expression of either of two different dominant negative k inase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells subs tantially inhibited the tumor promoter induced activation of Erks1 and 2 an d of AP-I measured by a collagenase-luciferase reporter. Multiple mutant Er k2 expressing clonal lines were also rendered non-responsive to induced neo plastic transformation. These observations, together with our recent findin g attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and /or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progre ssion model, and suggest the utility of Erks as a prevention target.