Breast cancer cells have lower activating protein 1 transcription factor activity than normal mammary epithelial cells.
To determine whether normal breast cells have different levels of activating protein 1 (AP-1) expression and activation relative to breast cancer cells, we have compared the level of c-Jun and c-Fos expression and AP-1 activity in human mammary epithelial cells (HMECs) at different stages of transformation (normal proliferating HMECs, immortal HMECs, oncogene-transformed HMECs, and breast cancer cell lines). These studies demonstrated that normal and immortal HMECs have a high basal level of expression of cJun and cFos and higher AP-1 DNA-binding and transcriptional activating activities than do oncogene-transformed HMECs or human breast cancer cells, with a gradual decrease in AP-1 transactivating activity as cells progress through the carcinogenesis pathway (normal > immortal > oncogene-transformed > cancer cell lines). The AP-1 activity in normal or immortal cells was not modulated by growth factor supplementation or oncogene overexpression, as it is in breast cancer cells. However, the addition of suramin, a nonspecific growth factor antagonist, did inhibit AP-1 in these HMECs, suggesting that this high level of AP-1 present in normal HMECs may be due to autocrine stimulation of growth factor pathways. The differences in AP-1 activity in normal and malignant breast cells may indicate that normal cells are more dependent on AP-1-mediated signals for their growth than are breast cancer cells.
Smith
L M
LM
Division of Cancer Prevention and Control, National Cancer Institute, Rockville, Maryland 20850, USA.
Birrer
M J
MJ
Stampfer
M R
MR
Brown
P H
PH
D001940:Breast / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000737:chemistry; D005260:Female; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D018808:Transcription Factor AP-1 / Q000032:analysis*; D014162:Transfection
D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor