Prevention of Breast Cell Transformation by Blockade of the AP-1 Transcription Factor
Abstract
In this study, we are investigating the role of AP-1 in controlling breast cell growth and transformation. We have previously demonstrated that normal human breast cells have high basal levels of AP-1 activity and that breast cancer cells express relatively low levels of AP-1 activity. We have also shown that AP-1 complexes are activated by peptide and steroid growth factors in normal and malignant breast cells. In this report, we now show that other peptide growth factors, including IGF-1, EGF, heregulin-Beta, and FGF, stimulate AP-1 activity in breast cancer cells. This growth factor-induced AP-1 activity can be suppressed by the expression of TAM67. The mitogenic pathways activated by serum and these growth factors depend on AP-1 to transduce proliferative signal. AP-1 blockade induced by the expression of TAM67 inhibits breast cancer cell growth mainly by delaying S phase entry, and inducing G1 cell cycle arrest. In the future, we will determine whether AP-1 blockade inhibits breast cell growth in vivo and whether AP-1 blockade prevents oncogene-induced transformation of breast cells. These results suggest that AP-1 is a promising target of future cancer therapeutic and preventive agents since blocking this critical transcription factor suppresses proliferation induced by multiple growth factors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA391107
Entities
People
- Powel H. Brown
Organizations
- Baylor College of Medicine