Abstract
The expression of several early-response genes and genes associated with malignant disease was assessed in the EMT-6/parent tumor and the EMT-6/CTX and EMT-6/CDDP in vivo resistant tumor lines growing as tumors or as monolayers in culture. In the absence of treatment the levels of mRNA for the genes c -jun, c -fos, c -myc, Ha-ras and p53 were increased in the EMT-6/CTX and EMT-6/CDDP as compared with the EMT-6/parent tumor, whereas the expression of erb-2 was similar in all three tumors. Although the cells from each of the three tumors show increased expression of early response genes after exposure to cisplatin (CDDP; 100 μM, 2 h) or 4-Hydroxypero-xycyclophosphamide (4-HC; 100 μM, 2 h) in culture, in mRNA extracted from tumor tissue these changes are absent or very small. Both C -jun and erb-2 were detectable in liver. There was increased expression of both of these genes in the livers of tumor-bearing animals as compared with non-tumor-bearing animals. The highest expression of both c -jun and erb-2 occurred in the livers of animals bearing the EMT-6/CDDP tumor. Treatment of the animals with CDDP or cyclophos-phamide, in general, resulted in increased expression of both genes at 6 h post treatment. The increased expression of these genes may impart metabolic changes in the tumors and/or hosts that contribute to the resistance of these tumors to specific antitumor alkylating agents.
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This work was supported by NIH grants PO1-38493 and RO1-50174.
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Chatterjee, D., Liu, C.JT., Northey, D. et al. Molecular characterization of the in vivo alkylating agent resistant murine EMT-6 mammary carcinoma tumors. Cancer Chemother. Pharmacol. 35, 423–431 (1995). https://doi.org/10.1007/s002800050257
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DOI: https://doi.org/10.1007/s002800050257