Tumor promotion resistant cells are deficient in AP-1 DNA binding, JunD DNA binding and JunD expression and form different AP-1-DNA complexes than promotion sensitive cells.
The JB6 cell culture model is used to identify molecular determinants of susceptibility to the promotion of neoplastic transformation. Clonal variants susceptible to transformation ('P+' cells) form numerous anchorage-independent colonies in soft agar upon treatment with the phorbol ester tumor promoter TPA, whereas resistant variants ('P-' cells) do not. We now report that there is significantly less binding of activator protein-1 (AP-1) to its DNA binding site in P- cells than in P+ cells. Gel supershift assays were performed to detect association of all seven AP-1 family members with their DNA binding site in TPA-treated and -untreated P+ and P- cells. Significantly lower DNA binding and protein expression of JunD were detected in P- cells than in P+ cells. c-Jun was detected in P+, but not P-, AP-1-DNA complexes, and c-Fos was detected in P-, but not P+, AP-1-DNA complexes. These and other phenotype-specific differences in abundance and composition of AP-1-DNA complexes may play a role in the resistance of P- cells to tumor promoter-induced transformation.
Bernstein
L R
LR
Texas A&M Health Science Center, Department of Pathology and Laboratory Medicine, College Station, 77843-1114, USA. lbernstein@tamu.edu
Walker
S E
SE
D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D017364:Collagenases / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D017931:DNA Primers; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D017364:Collagenases