BREAST-CANCER CELL INVASIVENESS - CORRELATION WITH PROTEIN-KINASE-C ACTIVITY AND DIFFERENTIAL REGULATION BY PHORBOL ESTER IN ESTROGEN RECEPTOR-POSITIVE AND RECEPTOR-NEGATIVE CELLS

Increased protein kinase C (PKC) activity in malignant breast tissue a nd in most aggressive breast cancer cell lines has suggested a possibl e role of PKC in breast carcinogenesis and tumor progression. We have investigated here the involvement of PKC in the in vitro invasiveness and motility of several breast cancer cell lines. Modulation of PKC ac tivity by treatment with a phorbol ester (TPA), drastically increased the invasiveness of 2 estrogen receptor-positive (ER+) lines (MCF7 and ZR 75.1), whereas it markedly decreased the invasiveness of 2 ER- cel l lines (MDA-MB-231 and MDA-MB-435). A PKC inhibitor (H7) reversed the TPA effects in MCF7 cells, whereas it mimicked TPA action in MDA-MB-2 31 cells. All of these effects of TPA also were observed to a similar extent for cell chemotaxis, and they were not dependent on protein neo -synthesis. In parallel, short TPA treatment induced cell spreading an d microtubule organization in MCF7 cells and inverse morphological cha nges in MDA-MB-231 cells. In ER+ cells, constitutive PKC activity and PKC alpha expression were very row as compared to ER-cells, and this c orrelated with the invasive potential of the cells. The opposed effect s of TPA in ER+ and ER-cells could be due to the abnormal TPA regulati on of PKC alpha observed in ER-cells. (C) 1998 Wiley-Liss, Inc.