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. 1991 Feb;63(2):237–241. doi: 10.1038/bjc.1991.56

Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes.

S Niimi 1, K Nakagawa 1, J Yokota 1, Y Tsunokawa 1, K Nishio 1, Y Terashima 1, M Shibuya 1, M Terada 1, N Saijo 1
PMCID: PMC1971793  PMID: 1997100

Abstract

NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c-H-ras genes, respectively. The IC50s of cisplatin, 4-hydroperoxycyclophosphamide, adriamycin, melphalan, and CPT-11 were significantly higher for NIH3T3-nm-1 abd pT22-3-nm-2 than for the parental NIH3T3 and N8 cells. Transfection with normal and activated C-H-ras oncogenes only led to increases in the IC50s of alkylating agents. There was no significant difference between the IC50s of N8 and those of NIH3T3 parental cells to any of these anticancer agents. These results strongly suggest that the expression of the c-myc gene plays a role in the acquisition of drug resistance. The c-myc gene may therefore provide us with an important clue in determining the mechanism of drug resistance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell D. R., Gerlach J. H., Kartner N., Buick R. N., Ling V. Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. J Clin Oncol. 1985 Mar;3(3):311–315. doi: 10.1200/JCO.1985.3.3.311. [DOI] [PubMed] [Google Scholar]
  2. Bradley G., Naik M., Ling V. P-glycoprotein expression in multidrug-resistant human ovarian carcinoma cell lines. Cancer Res. 1989 May 15;49(10):2790–2796. [PubMed] [Google Scholar]
  3. Burt R. K., Garfield S., Johnson K., Thorgeirsson S. S. Transformation of rat liver epithelial cells with v-H-ras or v-raf causes expression of MDR-1, glutathione-S-transferase-P and increased resistance to cytotoxic chemicals. Carcinogenesis. 1988 Dec;9(12):2329–2332. doi: 10.1093/carcin/9.12.2329. [DOI] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Cowan K. H., Batist G., Tulpule A., Sinha B. K., Myers C. E. Similar biochemical changes associated with multidrug resistance in human breast cancer cells and carcinogen-induced resistance to xenobiotics in rats. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9328–9332. doi: 10.1073/pnas.83.24.9328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeLorbe W. J., Luciw P. A., Goodman H. M., Varmus H. E., Bishop J. M. Molecular cloning and characterization of avian sarcoma virus circular DNA molecules. J Virol. 1980 Oct;36(1):50–61. doi: 10.1128/jvi.36.1.50-61.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695-1705.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gazdar A. F., Carney D. N., Nau M. M., Minna J. D. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 1985 Jun;45(6):2924–2930. [PubMed] [Google Scholar]
  9. Goldfarb M., Shimizu K., Perucho M., Wigler M. Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature. 1982 Apr 1;296(5856):404–409. doi: 10.1038/296404a0. [DOI] [PubMed] [Google Scholar]
  10. Hong W. S., Saijo N., Sasaki Y., Minato K., Nakano H., Nakagawa K., Fujiwara Y., Nomura K., Twentyman P. R. Establishment and characterization of cisplatin-resistant sublines of human lung cancer cell lines. Int J Cancer. 1988 Mar 15;41(3):462–467. doi: 10.1002/ijc.2910410325. [DOI] [PubMed] [Google Scholar]
  11. Kano T., Sakai M., Muramatsu M. Structure and expression of a human class pi glutathione S-transferase messenger RNA. Cancer Res. 1987 Nov 1;47(21):5626–5630. [PubMed] [Google Scholar]
  12. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  13. Ma D. D., Scurr R. D., Davey R. A., Mackertich S. M., Harman D. H., Dowden G., Isbister J. P., Bell D. R. Detection of a multidrug resistant phenotype in acute non-lymphoblastic leukaemia. Lancet. 1987 Jan 17;1(8525):135–137. doi: 10.1016/s0140-6736(87)91969-6. [DOI] [PubMed] [Google Scholar]
  14. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  15. Nakagawa K., Yokota J., Wada M., Sasaki Y., Fujiwara Y., Sakai M., Muramatsu M., Terasaki T., Tsunokawa Y., Terada M. Levels of glutathione S transferase pi mRNA in human lung cancer cell lines correlate with the resistance to cisplatin and carboplatin. Jpn J Cancer Res. 1988 Mar;79(3):301–304. doi: 10.1111/j.1349-7006.1988.tb01590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  17. Perucho M., Goldfarb M., Shimizu K., Lama C., Fogh J., Wigler M. Human-tumor-derived cell lines contain common and different transforming genes. Cell. 1981 Dec;27(3 Pt 2):467–476. doi: 10.1016/0092-8674(81)90388-3. [DOI] [PubMed] [Google Scholar]
  18. Roninson I. B., Chin J. E., Choi K. G., Gros P., Housman D. E., Fojo A., Shen D. W., Gottesman M. M., Pastan I. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4538–4542. doi: 10.1073/pnas.83.12.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rothberg P. G., Erisman M. D., Diehl R. E., Rovigatti U. G., Astrin S. M. Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies. Mol Cell Biol. 1984 Jun;4(6):1096–1103. doi: 10.1128/mcb.4.6.1096-1103.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  21. Schimke R. T. Gene amplification, drug resistance, and cancer. Cancer Res. 1984 May;44(5):1735–1742. [PubMed] [Google Scholar]
  22. Sklar M. D. Increased resistance to cis-diamminedichloroplatinum(II) in NIH 3T3 cells transformed by ras oncogenes. Cancer Res. 1988 Feb 15;48(4):793–797. [PubMed] [Google Scholar]
  23. Sklar M. D. The ras oncogenes increase the intrinsic resistance of NIH 3T3 cells to ionizing radiation. Science. 1988 Feb 5;239(4840):645–647. doi: 10.1126/science.3277276. [DOI] [PubMed] [Google Scholar]
  24. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  25. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  26. Toffoli G., Viel A., Tumiotto L., Buttazzi P., Biscontin G., Boiocchi M. Sensitivity pattern of normal and Ha-ras transformed NIH3T3 fibroblasts to antineoplastic drugs. Tumori. 1989 Oct 31;75(5):423–428. doi: 10.1177/030089168907500505. [DOI] [PubMed] [Google Scholar]
  27. Viola M. V., Fromowitz F., Oravez S., Deb S., Schlom J. ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma. J Exp Med. 1985 May 1;161(5):1213–1218. doi: 10.1084/jem.161.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]

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