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 acti vating protein 1 (AP-1) expression and activation relative to breast c ancer cells, we have compared the level of c-Jun and c-Fos expression and AP-1 activity in human mammary epithelial cells (HMECs) at differe nt stages of transformation (normal proliferating (HMECs, immortal HME Cs, oncogene-transformed HMECs, and breast cancer cell lines). These s tudies demonstrated that normal and immortal HMECs have a high basal l evel of expression of cJun and cFos and higher AP-1 DNA-binding and tr anscriptional activating activities than do oncogene-transformed HMECs or human breast cancer cells, with a gradual decrease in AP-1 transac tivating activity as cells progress through the carcinogenesis pathway (normal > immortal > oncogene-transformed > cancer cell lines). The A P-1 activity in normal or immortal cells was not modulated by growth f actor supplementation or oncogene overexpression, as it is in breast c ancer cells. However, the addition of suramin, a nonspecific growth fa ctor antagonist, did inhibit. AP-1 in these HMECs, suggesting that thi s high level of AP-1 present in normal HMECs mag be due to autocrine s timulation of growth factor pathways. The differences in AP-1 activity in normal and malignant breast cells may indicate that normal cells a re more dependent on AP-1-mediated signals for their growth than are b reast cancer cells.