Elevated expression of DNA ligase I in human cancers

Daekyu Sun, R. Urrabaz, M. Nguyen, J. Marty, S. Stringer, E. Cruz, L. Medina-Gundrum, S. Weitman

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: Human DNA ligase I plays an essential role in DNA replication, recombination, and repair by catalyzing the formation of phosphodiester bonds between adjacent 5′-phosphoryl and 3′-hydroxyl termini at single breaks in duplex DNA molecules. DNA ligase I is responsible for the majority of DNA ligase activity present in proliferating cells among four different forms of DNA ligases, designated DNA ligase I, II, III, and IV. In this study, we were interested in comparing DNA ligase I level in human tumors versus normal tissues and in studying whether the inhibition of DNA ligase I could lead to tumor cell death. Experimental Design: DNA ligase I level was measured by Western immunoblot assay in various human malignant tumor specimens and benign tissues obtained from patients, in peripheral blood lymphocytes obtained from healthy donors, and in human tumors grown in nude mice. We also have designed antisense oligonucleotides (ODNs) targeting the mRNA of DNA ligase I and tested whether DNA ligase I antisense ODNs could control tumor cell growth. Results: The amount of DNA ligase I enzyme in malignant tumors was considerably higher than that in benign normal tissues and peripheral blood lymphocytes. The level of DNA ligase I in human tumors grown in nude mice was also very high, and the expression of DNA ligase I appears to be constitutive during in vivo tumor development. We have observed that DNA ligase I antisense ODN inhibited tumor cell growth in a dose-response manner, but nonspecific control ODNs had little effect on the growth of the same cell lines. Conclusions: The presence of DNA ligase I at higher levels in human tumors than in benign normal tissues and normal peripheral lymphocytes suggests DNA ligase I plays more of a role in proliferating cells than in resting cells. These results, together with our finding that DNA ligase I antisense ODNs can suppress tumor cell proliferation, warrant the design and testing of human DNA ligase I inhibitors as new anticancer agents.

Original languageEnglish (US)
Pages (from-to)4143-4148
Number of pages6
JournalClinical Cancer Research
Volume7
Issue number12
StatePublished - 2001
Externally publishedYes

Fingerprint

Neoplasms
DNA Ligases
DNA Ligase ATP
Lymphocytes
Nude Mice
Growth
Recombinational DNA Repair
Antisense Oligonucleotides
DNA Replication
DNA Repair
Hydroxyl Radical
Antineoplastic Agents
Cell Death
Research Design
Western Blotting
Cell Proliferation
Tissue Donors
Cell Line
Messenger RNA
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sun, D., Urrabaz, R., Nguyen, M., Marty, J., Stringer, S., Cruz, E., ... Weitman, S. (2001). Elevated expression of DNA ligase I in human cancers. Clinical Cancer Research, 7(12), 4143-4148.

Elevated expression of DNA ligase I in human cancers. / Sun, Daekyu; Urrabaz, R.; Nguyen, M.; Marty, J.; Stringer, S.; Cruz, E.; Medina-Gundrum, L.; Weitman, S.

In: Clinical Cancer Research, Vol. 7, No. 12, 2001, p. 4143-4148.

Research output: Contribution to journalArticle

Sun, D, Urrabaz, R, Nguyen, M, Marty, J, Stringer, S, Cruz, E, Medina-Gundrum, L & Weitman, S 2001, 'Elevated expression of DNA ligase I in human cancers', Clinical Cancer Research, vol. 7, no. 12, pp. 4143-4148.
Sun D, Urrabaz R, Nguyen M, Marty J, Stringer S, Cruz E et al. Elevated expression of DNA ligase I in human cancers. Clinical Cancer Research. 2001;7(12):4143-4148.
Sun, Daekyu ; Urrabaz, R. ; Nguyen, M. ; Marty, J. ; Stringer, S. ; Cruz, E. ; Medina-Gundrum, L. ; Weitman, S. / Elevated expression of DNA ligase I in human cancers. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 12. pp. 4143-4148.
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