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M_r 85,000 Membrane Protein Specifically Expressed in Adriamycin-resistant Human Tumor Cells¹

Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan

For the characterization of membrane changes related to Adriamycin resistance in tumor cells, we have developed monoclonal antibodies against Adriamycin-resistant human myelogenous leukemia K562 (K562/ADM). In addition to the monoclonal antibodies which recognize P-glycoprotein, we have obtained two monoclonal antibodies (designated MRK4 and MRK20) which recognize an M_r 85,000 membrane protein. Using MRK20 as a probe, we have studied the expression of the M_r 85,000 protein in various human multidrug-resistant and -sensitive cell lines. The M_r 85,000 protein was overexpressed in K562/ADM and in a human ovarian cancer cell line resistant to Adriamycin, 2780^AD. The protein, if any, was not detected in other drug-resistant human cell lines such as colchicine-resistant KB cells (KB-C4), vinblastine-resistant CEM cells (CEM/VLB₁₀₀), and vincristine-resistant K562 cells (K562/VCR). We have isolated subclones of K562/ADM cells which express different amounts of the M_r 85,000 protein. The expression of the M_r 85,000 protein diminished when the cells were not kept in Adriamycin, and increased when the clones were kept in the presence of Adriamycin. In contrast, the expression of P-glycoprotein remained constant whether in the presence or absence of Adriamycin during these experiments. These findings suggest that the M_r 85,000 membrane protein is closely related to the resistant mechanism specific to Adriamycin resistance, which is different from that of the pleiotropic drug resistance.

¹ This work was supported by Grants from the Ministry of Education, Science and Culture, and the Ministry of Health and Welfare, Japan and party by the Society for Promotion of Cancer Research, Japan, and Mochida Memorial Foundation.

² To whom requests for reprints should be addressed.

Received 3/ 7/88. Revised 8/18/88. Accepted 9/ 8/88.