Aberrant Synthesis and Secretion of a Human Epidermal Growth Factor-Like Immunoreactive Factor by Human Breast Cancer Cells

抄録

Previously we reported that human breast cancer cell strain MCF-7 released an extremely large amount of a human epidermal growth factor (hEGF)-like immunoreactive factor (designated as MCF-7 EGF) into the culture medium. In this paper, we examined in detail the synthesis and secretion of MCF-7 EGF by the cells. Our enzyme immunoassay system for hEGF distinguished MCF-7 EGF from hEGF or transforming growth factor type-α. The amount of MCF-7 EGF secreted increased linearly up to 24h. Secretion of the molecule was inhibited by cycloheximide and actinomycin D, but not by cytosine arabinoside, suggesting that synthesis of MCF-7 EGF requires DNA transcription but not DNA replication. A significant amount of MCF-7 EGF was detected in the cells. Intracellular MCF-7 EGF showed the same properties as the extracellular form in its antigenicity, molecular weight, and isoelectric point. In the presence of the ionophore monensin, the amount of extracellular MCF-7 EGF decreased greatly and that of intracellular MCF-7 EGF increased, indicating that MCF-7 EGF is secreted from its intracellular site via the Golgi apparatus into the culture medium. β-Estradiol specifically stimulated production of MCF-7 EGF, revealing hormonal regulation of synthesis of the factor. Possible involvement of MCF-7 EGF in the development and progress of mammary tumors is also discussed.