Reduction of epidermal growth factor binding in human breast cancer cell lines by an alkyl-lysophospholipid.
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 micrograms/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 micrograms/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.
Kosano
H
H
Third Department of Internal Medicine, National Defense Medical College, Japan.
Takatani
O
O
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D010713:Phosphatidylcholines / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C