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Developmental Therapeutics Program (DTP)
Last Updated: 05/08/15

Cell Line NCI/ADR-RES is an Ovarian tumor cell line, not a Breast line.

In 1986 Batist et al. (1) developed an adriamycin-resistant cell line, termed MCF-7/ADR-RES intended to be derived from the breast tumor cell line MCF-7. This cell line expresses high levels of MDR1 and P-glcyoprotein (2, 3), and given it’s utility in identifying compounds subject to multi-drug resistance, was introduced into the NCI 60 human tumor cell line anti-cancer drug screen. However, in 1998, Scudiero et al (4) reported that DNA fingerprinting of MCF-7 and MCF-7/ADR-RES lines were inconsistent with these two lines having been derived from the same individual. Thus MCF-7/ADR-RES was renamed NCI/ADR-RES.

New data sheds light on the origin of the NCI/ADR-RES line. Spectral karyotyping of the 59 cell lines currently in the drug screen panel demonstrates that the Ovarian tumor cell line OVCAR-8 shares a large number of karyotypic abnormalities with the NCI/ADR-RES line (5). These abnormalities include many complex chromosomal rearrangements involving multiple chromosomes. These rearrangements are not shared by any of the other cell lines in the panel. Both of these cell lines exhibit profound chromosomal instability, thus even though they share many rearrangements, there are also considerable differences in their karyotypes. To see images of the karyotypes, click here. Ideograms for all 59 cell lines can be viewed at the NCBI SKY database at: http://www.ncbi.nlm.nih.gov/sky/.

In support of the karyotypic analysis, NCI obtained DNA fingerprinting analysis on these cell lines. Orchid Cellmark analyzed short tandem repeats by PCR at 14 loci. OVCAR-8 and NCI/ADR-RES are identical at 13/14 loci. Data from the remaining locus are consistent with loss of heterozygosity in NCI/ADR-RES. In contrast, MCF-7 fingerprinting demonstrated it was unrelated to OVCAR-8 or NCI/ADR-RES. Thus DNA fingerprinting support OVCAR-8 and NCI/ADR-RES as being derived from the same individual.

Furthermore, gene expression patterns indicate very similar patterns of gene expression, apart from the high levels of MDR1 and Pgp seen in NCI/ADR-RES. Cluster analysis of microarray expression data showed OVCAR-8 and NCI/ADR-RES clustering tightly with one another (6).

More recently single nucleotide polymorphism (SNP) array analysis confirmed that the NCI/ADR-RES line is derived from the same individual as the ovarian line OVCAR-8 (Garraway LA, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005 Jul 7;436(7047):117-22.; http://www.sanger.ac.uk/genetics/CGP/NCI60/).

The conclusion that must be drawn is that the NCI/ADR-RES line is in fact derived from the ovarian cell line OVCAR-8.

References

  1. Batist G, Tulpule A, Sinha BK, Katki AG, Myers CE, Cowan KH. Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J Biol Chem. 1986 Nov 25;261(33):15544-9.
  2. Alvarez M, Paull K, Monks A, Hose C, Lee JS, Weinstein J, Grever M, Bates S, Fojo T. Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute Anticancer Drug Screen. J Clin Invest. 1995 May;95(5):2205-14.
  3. Lee JS, Paull K, Alvarez M, Hose C, Monks A, Grever M, Fojo AT, Bates SE. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Mol Pharmacol. 1994 Oct;46(4):627-38.
  4. Scudiero DA, Monks A, Sausville EA. Cell line designation change: multidrug-resistant cell line in the NCI anticancer screen. J Natl Cancer Inst. 1998 Jun 3;90(11):862.
  5. Roschke AV, Tonon G, Gehlhaus KS, McTyre N, Bussey KJ, Lababidi S, Scudiero DA, Weinstein JN, Kirsch IR. Karyotypic Complexity of the NCI-60 Drug-Screening Panel. Cancer Res. 2003 Dec 15;63(24):8634-8647.
  6. Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet. 2000 Mar;24(3):227-35