SUPPRESSION OF DIACYLGLYCEROL LEVELS BY ANTIBODIES REACTIVE WITH THE C-ERBB-2 (HER-2 NEU) GENE-PRODUCT P185(C-ERBB-2) IN BREAST AND OVARIAN-CANCER CELL-LINES/

Seven of 10 murine monoclonal antibodies reactive with the extracellul ar domain of p185(c-erbB-2) inhibited the anchorage independent growth of the SKBr3 breast cancer cell line that overexpressed p185(c-erbB-2 ). Significant inhibition (56-72%) of diacylglycerol (DAG) levels (P < 0.0001) was observed with the 10 antibodies that inhibited SKBr3 grow th (RC1, NB3, RC6, PB3, 741F8, DB5, ID5), whereas the 3 antibodies (TA 1, 520C9, 454C11) that failed to inhibit SKBr3 growth also failed to a ffect DAG levels. Thus, DAG levels correlated with antibody-mediated g rowth regulation for each of the 10 monoclonal reagents, Antibody-indu ced inhibition of anchorage-independent growth of SKBr3 could be rever sed by incubation with phorbol myristate acetate, The ID5 antibody inh ibited growth of the SKBr3, SKOv3, and OVCA 432 tumor cell lines, but not of OVCA 420, OVCA 429, and OVCA 433. DAG levels were significantly decreased after ID5 treatment of the SKBr3 and SKOv3 cell lines, but not the OVCA 420, OVCA 429, and OVCA 433 lines. In the 432 line, there was a decrease which did not reach significance. Consequently, change s in DAG levels correlated with growth regulation in 5 of 6 breast and ovarian carcinoma cell lines tested with a trend toward correlation i n the sixth. Decreases in DAG may be one mediator of the growth regula tory signals produced by anti-p185(c-erbB-2) antibodies, (C) 1998 Acad emic Press.