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Reduction of Epidermal Growth Factor Binding in Human Breast Cancer Cell Lines by an Alkyl-Lysophospholipid

Third Department of Internal Medicine, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359 Japan

The effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH₃), an alkyl lysophospholipid derivative, on the binding of epidermal growth factor (EGF) to human breast cancer cell lines (MCF-7, ZR-75-1, and BT-20), the human epidermoid cancer cell line (A431), and the rat fibroblast cell line (NIH3T3) were investigated. The addition of 10 µg/ml ET-18-OCH₃ to the growth medium reduced the binding of EGF to hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) and A431 but did not change that to the hormone-independent breast cancer cell line (BT-20). ET-18-OCH₃ suppressed the EGF-binding prior to the onset of its inhibitory action on cell growth in MCF-7 and ZR-75-1. Scatchard plot analysis demonstrated that ET-18-OCH₃ reduced the number of EGF receptor sites without affecting the affinity of EGF receptors in MCF-7 and ZR-75-1. Both EGF-binding and cell growth in NIH3T3 were not changed by treatment with 10 µg/ml ET-18-OCH₃. These results suggest that ET-18-OCH₃ inhibits the growth of hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) by reducing the binding capacity of EGF receptors and consequently by disturbing the transfer of a variety of growth-promoting signals.

¹ To whom requests for reprints should be addressed.

Received 10/14/87. Revised 5/ 2/88. Revised 7/11/88. Accepted 7/15/88.