Prevention of Breast Cell Transformation by Blockade of the AP-1 Transcription Factor.
Abstract
We are investigating the role of the AP-l transcription complex in regulating the growth of normal and malignant breast cells. We have determined the levels of cJun and cFos protein expression and AP-l transcriptional activity in normal HMECs, immortalized HMECs, oncogene-transformed HMECs, and breast cancer cell lines, and have determined the relative sensitivity of these different cells to a specific AP-1 inhibitor. These studies demonstrated that there is a progressive decline in basal A')- 1 activity as human mammary epithelial cells progress through the carcinogenesis pathway (normal HMEC->immortal HMEC->oncogene-transformed HMEC->breast cancer cell). Stimulation of A')- 1 activity by EGF was observed in immortal, oncogene-transformed HMEC, and breast cancer cells but not normal HMECs. Normal HMECs, which had the highest AP-l activity, were most sensitive to AP-l inhibition, immortal HMEC, which have an intermediate A')- 1 activity, were moderately sensitive, and breast cancer cells, having the lowest AP-l activity, were relatively resistant to AP-1 blockade. This data suggests that as human mammary epithelial cells progress towards malignancy they become less dependent on AP- I transcriptional activity for proliferation. In ongoing studies we are now investigating whether the transformed phenotype of human breast cells depends on AP- 1 activity. These studies will define the role of AP-l in regulating growth and transformation of human breast cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA337856
Entities
People
- Powel Brown
Organizations
- University of Texas Health Science Center at San Antonio