Sugimoto Y, Okochi E, Hamada H, Oh-hara T, Tsuruo T
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Biochem Biophys Res Commun. 1990 Jun 15;169(2):686-91. doi: 10.1016/0006-291x(90)90385-z.
To characterize the membrane changes related to adriamycin (ADM) resistance in tumor cells, we have developed monoclonal antibodies against an ADM-resistant subline of human myelogenous leukemia K562 (K562/ADM), and reported the overexpression of P-glycoprotein and 85-kDa protein as determined by the antibodies. In the present study, we have established a monoclonal antibody, MRK18, with higher reactivity to K562/ADM than to K562. MRK18 also showed higher reactivity to other human ADM-resistant lines, 2780AD and Hattori/ADM, than the corresponding parental lines. MRK18 also reacted to human breast cancer MCF-7 and human T-lymphoma CCRF-CEM which have never been exposed to anticancer agents in culture. MRK18 recognized a 300-kDa membrane protein of K562/ADM and MCF-7 and inhibited the growth of these cell lines in culture. These results indicate an induction of the 300-kDa protein during the development of ADM resistance.
为了描述肿瘤细胞中与阿霉素(ADM)耐药相关的膜变化,我们制备了针对人髓性白血病K562的阿霉素耐药亚系(K562/ADM)的单克隆抗体,并报道了用这些抗体检测到的P-糖蛋白和85 kDa蛋白的过表达。在本研究中,我们制备了一种单克隆抗体MRK18,它对K562/ADM的反应性高于对K562的反应性。MRK18对其他人类阿霉素耐药细胞系2780AD和Hattori/ADM的反应性也高于相应的亲本细胞系。MRK18还与在培养中从未接触过抗癌药物的人乳腺癌MCF-7和人T淋巴瘤CCRF-CEM发生反应。MRK18识别K562/ADM和MCF-7的一种300 kDa膜蛋白,并抑制这些细胞系在培养中的生长。这些结果表明在阿霉素耐药形成过程中诱导产生了300 kDa蛋白。