REGULATION OF THE EXPRESSION OF ALKALINE-PHOSPHATASE IN A HUMAN BREAST-CANCER CELL-LINE

Treatment of the cultured human breast-cancer cells BC-M1 with dexamet hasone induced a placental-type alkaline phosphatase (ALP). Both the A LP activity and the mRNA level in the cells were increased. The induct ion of ALP activity by dexamethasone was time- and dose-dependent. The accumulation of ALP mRNA was inhibited by both actinomycin D and cycl oheximide, indicating that its induction is a complex event and may in volve other regulatory proteins. Retinoic acid showed opposing effects with dexamethasone on the expression of alkaline phosphatase. Retinoi c acid (RA) and phorbol 12-myristate 13-acetate also substantially red uced the dexamethasone-induced expression of ALP. Studies on thermosta bility and sensitivity to various amino acid inhibitors indicated that the BC-M1 ALP is most similar to the placental form. Northern hybridi zation analysis also revealed that ALP mRNA transcripts in BC-M1 and t erm placenta are similar in size and are distinct from that of the pla cental-like mRNA transcript in choriocarcinoma cells. Analysis of the degradation of BC-M1 ALP mRNA showed a similar half-life of 27 h in th e untreated and in dexamethasone- or RA-treated cells. These findings demonstrated that the induction of ALP in BC-M1 cells by dexamethasone is mainly due to the increase in the transcription of the ALP gene.