Abstract
Drug resistance in human cancer cells is one of the most, if not the most, important factors that prevents the successful treatment of cancer in patients. At the time of diagnosis, many tumors are not curable and often not responsive to cancer chemotherapy drugs. The majority of tumors, that are curable with chemotherapy, such as acute lymphocytic leukemia, Burkitt’s lymphoma, Hodgkin’s disease, choriocarcinoma, and aggressive lymphomas with diffuse histology, tend to occur in younger patients. The tumors that occur predominately in older patients, such as colorectal, lung, breast, and prostate, tend to be less responsive and less curable with chemotherapy alone. The etiology of these tumors is probably related to long-term carcinogen exposure, and this may explain the predominance in older patients. The mechanisms underlying this form of resistance are not completely understood, but work by Fairchild et al. [1] demonstrated remarkable similarities between the biochemical characteristics of de novo drug resistance in carcinogen-induced rat liver cancer cells and in multidrug-resistant human breast cancer cells. Thus, there may be similar mechanisms between carcinogen-induced drug resistance, which occurs more commonly in the elderly, and multidrug resistance that develops through exposure to anticancer drugs.
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References
Fairchild, C.R., Ivy, S.P., Rushmore, T., Lee, G., Koo, P., Goldsmith, M.E., Myers, C.E., Farber, E. and Cowan, K.H. (1987). Carcinogen-induced MDR overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas. Proc. Natl. Acad. Sci. USA 84:7701–7705.
Rogan, A.M., Hamilton, T.C., Young, R.C., Klecker, R.W. and Ozols, R.F. (1984). Reversal of adriamycin resistance by verapamil in human overian cancer. Science 224:994–996.
Tsuruo, T., Iida, H., Tsukagoshi, S. and Sakurai, Y. (1983). Potentiation of vincristine and adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors. Cancer Res. 43:2267–2272.
Kartner, N., Riordan, J.R. and Ling, V. (1983). Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science 221:1285–1288.
Myers, M.B. and Biedler, J.L. (1981). Increased synthesis of a low molecular weight protein in vincristine-resistant cells. Biochem. Biophys. Res. Comm. 99:228–235.
Safa, A.R., Glover, C.J., Myers, M.B., Biedler, J.L. and Felsted, R.L. (1986). Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J. Biol. Chem. 261:6137–6140.
Cornwell, M.M., Safa, A.R., Felsted, R.L., Gottesman, M.M. and Pastan, I. (1986). Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170 kDa protein detected by photoaffinity labeling. Proc. Natl. Acad. Sci. USA 83:3847–3850.
Mori, T., Tokai, Y., Minakuchi, R., Yu, B. and Nishizuka, Y. (1980). Inhibitory action of chlorpromazine, dibucaine, and other phospholipid interacting drugs on calcium-activated, phospholipid-dependent protein kinase. J. Biol. Chem. 255:8378–8380.
Fine, R.L., Patel, J., Allegra, C.J., Curt, G.A., Cowan, K.H., Ozols, R.F., Lippman, M.E., McDevitt, R. and Chabner, B.A. (1985). Increased phosphorylation of a 20,000 new protein in pleiotropic drug-resistant MCF-7 human breast cancer cell lines. Proc. Am. Assoc. Cancer Res. 26:345.
Fine, R.L., Carmichael, J., Patel, J., Carney, D.N., Gazdar, A., Curt, G.A., Minna, J.D. and Chabner, B.A. (1986). Increased phosphorylation of a 20-kD protein is associated with pleiotropic drug resistance (PDR) in human small-cell lung cancer (SCLC) lines. Proc. Am. Soc. Clin. Oncol. 5:17.
Fine, R.L., Patel, J. and Chabner, B.A. (1988). Phorbol esters induce multidrug resistance in human breast cancer cells. Proc. Natl. Acad. Sci. USA 85:582–586.
Cowan, K.H., Goldsmith, M.E., Levine, R.M., Aitken, S.C., Douglass, E., Clendeninn, N., Nienhuis, A.W. and Lippman, M.E. (1982). Dihydrofolate reductase gene amplification and possible rearrangement in estrogen-responsive methotrexate-resistant human breast cancer cell lines. J. Biol. Chem. 257:15079–15086.
Karle, J., Cowan, K.H. and Cysyk, R. (1986). Uracil nucleotide synthesis in a human breast cancer line (MCF-7) and in two drug-resistant sublines that contain increased levels of enzymes of the de novo pyrimidine pathway. Mol. Pharmacol. 30:136–141.
Patel, J., Marangos, P.J., Heydorn, W.E., Chang, B., Verma, A. and Jacobowitz, D. (1983). S-100 mediated inhibition of brain phosphorylation. J. Neurochem. 41:1040–1045.
Kishimoto, A., Kajikawa, N., Shiota, M. and Nishizuka, Y. (1983). Proteolytic activation of calcium-activated phospholipid-dependent protein kinase by calcium-dependent neutral protease. J. Biol. Chem. 258:1156–1164.
Myers, M. and Biedler, J.L. (1981). Increased synthesis of a low molecular weight protein in vincristine-resistant cells. Biochem. Biophys. Res. Comm. 99:228–235.
Marsh, W. and Center, M.S. (1985). In vitro phosphorylation and the identification of multiple protein changes in membranes of Chinese hamster lung cells resistant to adriamycin. Biochem. Pharmacol. 34:4180–4184.
Weisenthal, L.M., Dill, P., Kurnick, N. and Lippman, M.E. (1983). Comparison of dye exclusion on assays with a clonogenic assay in the determination of drug-induced cytotoxicity. Cancer Res. 43:258–264.
Rebois, R.V. and Patel, J. (1985). Phorbol ester causes desensitization of gonadotropin-responsive adenylate cyclase in a murine Leydig tumor cell line. J. Biol. Chem. 260:8026–8931.
Fine, R.L., Patel, J., Carmichael, J., Cowan, K., Curt, G.A. and Chabner, B.A. (1986). Phosphoprotein markers and protein kinase C changes in human drug-resistant cancer cells. In Vitro 22:56A.
Nishizuka, Y. (1986). Studies and perspectives of protein kinase C. Science 233:305–312.
Louie, K.G., Hamilton, T.C., Winkler, M.A., Behrens, B.C., Tsuruo, T., Klecker, R.W., McCoy, W.M., Grotzingen K.R., Myers, C.E., Young, R.C and Ozols, R.F. (1986). Adriamycin accumulation and metabolism in adriamycin sensitive and resistant human ovarian cancer cell lines. Biochem. Pharmacol. 35:467–472.
Hamada, H., Hagiwara, K.I., Nakajima, T. and Tsuruo, T. (1987). Phosphorylation of the Mr 170,000 to 180,000 glycoprotein specific to multidrug-resistant tumor cells: Effects of verapamil, trifluoperazine and phorbol esters. Cancer Res. 47:2860–2865.
Ido, M., Asao, T., Sakurai, M., Inagaki, M., Saito, M. and Hidaka, H. (1986). An inhibitor of protein kinase C, l-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) inhibits TPA-induced reduction of vincristine uptake from P388 murine leukemia cells. Leuk. Res. 10:1063–1067.
Fine, R.L., Jett, M., Cowan, K.H., Weiss, R.B. and Chabner, B.A. (1987). Increased uptake of 3H-inositol and incorporation into phosphatidyl-inositols (PI) and hydrolysis of PI in multidrug-resistant MCF-7 cells. Proc. Am. Assoc. Cancer Res. 28:291.
Jett, M., Fine, R.L., Jelsema, C, Cowan, K.H. and Chabner, B.A. (1988). The signal transduction cascade is more responsive to stimulation in multidrug-resistant MCF-7 breast cancer cells than in the wild-type cells. Proc. Am. Assoc. Cancer Res. 29:20.
Jett, M., Fine, R.L., Cowan, K. and Chabner, B.A. (1987). Plant phosphatidylinositol is more cytotoxic to multidrug-resistant breast cancer cells than to the parent cells. Proc. Am. Assoc. Cancer Res. 28:284.
Fine, R.L., Monks, A., Patel, J., Jett, M., Ahn, C., Anderson, W., Shoemaker, R. and Chabner, B.A. (1988). Staurosporine, a potent inhibitor of protein kinase C, is equally toxic to sensitive and multidrug-resistant human cancer cells. Proc. Am. Assoc. Cancer Res. 29:301.
Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D. and Ullrich, A. (1986). The complete primary structure of protein kinase C—the major phorbol ester receptor. Science 233:853–859.
Kikkawa, U., Ono, Y., Okita, K., Fujii, T., Asaoka, Y., Sekiguchi, K., Kosaka, Y., Igarashi, K. and Nishizuka, Y. (1987). Identification of the structures of multiple subspecies of protein kinase C expressed in rat brain FEBS Letters 217:227–231.
Huang, F.L., Yoshida, Y., Nakabayashi, H. and Huang, K.P. (1987). Differential distribution of protein kinase C isozymes in the various regions of brain. J. Biol. Chem. 262:15714–15720.
Shearman, M.S., Naor, Z., Kikkawa, U. and Nishizuka, Y. (1987). Differential expression of multiple protein kinase C subspecies in rat central nervous tissue. Biochem. Biophys. Res. Commun. 147:911–919.
Ahn, C.H., Fine, R.L. and Anderson, W.B. (1988). Possible involvement of protein kinase C in the modulation of multidrug resistance. Proc. Am. Assoc. Cancer Res. 29:297.
Aquino, A., Niu, C. and Glazer, R.I. (1988). Altered expression of protein kinase C isoforms in multidrug-resistant cells. Proc. Am. Assoc. Cancer Res. 29:296.
Aftab, D.T. and Hait, W.N. (1988). Multiple forms of protein kinase C in multidrug-resistant MCF-7 human breast cancer cells. Proc. Am. Assoc. Cancer Res. 29:359.
Vickers, P.J., Dickson, R.B., Shoemaker, R. and Cowan, K.H. (1988). Multidrug-resistant MCF-7 human breast cancer cells display hormone-dependent tumor growth in vivo. Proc. Am. Assoc. Cancer Res. 29:314.
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© 1989 Kluwer Academic Publishers
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Fine, R.L., Jett, M., Patel, J., Carmichael, J., Ahn, CH. (1989). Phosphoprotein, protein kinase C, and second-messenger system changes in human multidrug-resistant cancer cells. In: Ozols, R.F. (eds) Drug Resistance in Cancer Therapy. Cancer Treatment and Research, vol 48. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1601-5_8
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DOI: https://doi.org/10.1007/978-1-4613-1601-5_8
Publisher Name: Springer, Boston, MA
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