Effects of vinorelbine on epidermal growth factor-receptor binding of human breast cancer cell lines in vitro.
Epidermal Growth Factor (EGF) is a mitogenic peptide that binds to surface membrane receptors (EGFR) of breast cancer cells. After binding, secondary transmitter molecules are activated by tyrosine phosphorylation of the intracellular receptor domaine. The activity of the EGF/EGFR system can be modulated by a variety of chemically unrelated compounds including cytostatic agents. The purpose of our present study was to determine the effects of vinorelbine, a novel semisynthetic vinca alkaloid on EGF receptor binding on human breast cancer cells. We have found that MDA-231 and MDA-468 cells bind substantially more [125I]-EGF after preincubation with vinorelbine. This effect was concentration- and time-dependent reaching a maximum at 100 ng/ml and 24 h incubation. Subsequent experiments showed an increase in the rate of EGF binding as well as maximal binding capacity. Scatchard analysis of binding experiments under equilibrium conditions indicated that this was mainly due to an increase in the number of apparent EGF binding sites. Modulation of EGF receptor binding by vinorelbine was not detectable when isolated membranes were used indicating that intact cytoplasmatic mechanisms are required for the upregulation of EGF receptors.
Depenbrock
H
H
Medical Department, Technische Universität München, Germany.
Shirvani
A
A
Rastetter
J
J
Hanauske
A R
AR
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D066246:ErbB Receptors; D000077235:Vinorelbine