Skip NavigationSkip to Content
Return Return to Search Results

Topoisomerase I levels in the NCI-60 cancer cell line panel determined by validated ELISA and microarray analysis and correlation with indenoisoquinoline sensitivity

  1. Author:
    Pfister, T. D.
    Reinhold, W. C.
    Agama, K.
    Gupta, S.
    Khin, S. A.
    Kinders, R. J.
    Parchment, R. E.
    Tomaszewski, J. E.
    Doroshow, J. H.
    Pommier, Y.

  2. Author Address

    Pfister, Thomas D.; Khin, Sonny A.; Kinders, Robert J.; Parchment, Ralph E.] Natl Canc Inst, Sci Applicat Int Corp Frederick Inc, Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, Frederick, MD 21702 USA. [Reinhold, William C.; Agama, Keli, Gupta, Shalu, Doroshow, James H.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
    1. Year: 2009
  2. Journal: Molecular Cancer Therapeutics
    1. 8
    2. 7
    3. Pages: 1878-1884
  4. Type of Article: Article
  1. Abstract:

    Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been used as a biomarker for chemotherapeutic efficacy. In this study, we report the development and validation of a two-site enzyme chemiluminescent immunoassay for Top1, which we used to measure Top1 levels in the NCI-60 cancer cell line panel. Top1 levels ranged from 0.9 to 9.8 ng/mL/mu g protein extract in these cell lines. Levels varied both within and between cancer types but were generally highest in colon cancer and leukemia cell lines and lowest in central nervous system and renal cancer cell lines. Top1 mRNA levels in the NCI-60 cell lines were also measured by microarray, mRNA values generally showed a good correlation with protein levels (Pearson correlation = 0.8). When these expression levels were compared with the activity of the indenoisoquinoline class of Top1 inhibitors across the NCI-60 cell panel, low levels of Top1 were associated with increased resistance to these drugs. The results of our studies indicate that our Top1 assay can be used to quantify Top1 levels in untreated cells as well as cells treated with Top1 inhibitors and that the assay has the potential to be adapted for use in predicting clinical response to Top1-active antineoplastic agents. [Mol Cancer Ther 2009,8(7):1878-84]

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1158/1535-7163.mct-09-0016
  3. PMID: 19584232

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel