Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):156-61.

Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells.

Author information

1
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.

Abstract

The JB6 mouse epidermal cell system, which includes tumor promotion-sensitive (P+) and tumor promotion-resistant (P-) cells, is a well-established and extensively used cell culture model for studying the mechanism of late-stage tumor promotion. Tumor promoters, such as 12-O-tetradecanoylphorbol 13-acetate (TPA) or epidermal growth factor (EGF), induce high levels of activator protein 1 (AP-1) activity and large, tumorigenic, anchorage-independent colonies in soft agar at a high frequency in JB6 P+ cells, but not in JB6 P- cells. We report here a molecular explanation for the defect in the AP-1 activation and promotion-resistant phenotype of P- cells. We demonstrate that the lack of AP-1 activation and cell transformation responses to TPA and EGF in P- cells appears attributable to the low level of mitogen-activated protein kinase (MAPK) (extracellular signal-regulated protein kinase, Erk) in these cells. TPA and EGF induce transactivation of AP-1 activity in P+ cells but not in P- cells. Nonphosphorylated forms and TPA- or EGF-induced phosphorylated forms of Erks (Erk1 and Erk2) in P- cells were much lower than those in P+ cells. Stable transfection of wild-type MAPK (Erk2) into P- cells restored its response to TPA and EGF for both AP-1 activation and cell transformation. These results suggest that the shortage of MAPK (Erk1 and Erk2) appears to be an important contributor to the tumor promotion-resistant phenotype in JB6 cells.

PMID:
9419345
PMCID:
PMC18158
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center