Effects of ectopic expression of NGAL on doxorubicin sensitivity

William H. Chappell, Stephen L. Abrams, Giuseppe Montalto, Melchiorre Cervello, Alberto M. Martelli, Saverio Candido, Massimo Libra, Jerry Polesel, Renato Talamini, Ralph Arlinghaus, Linda S. Steelman, James A. McCubrey

Research output: Contribution to journalArticle

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL expression is detected in response to various chemotherapeutic drugs including doxorubicin and docetaxel. We were interested in the roles of NGAL expression in cancer and whether it is associated with chemotherapeutic drug resistance. In the present study, we investigated whether increased NGAL expression led to resistance to the chemotherapeutic drug doxorubicin in normal breast epithelial cells (MCF-10A), breast cancer cells (MCF-7), and colorectal cancer cells (HT-29). We infected the various cell lines with a retrovirus encoding NGAL which we constructed. Increased NGAL expression was readily detected in the NGAL-infected cells but not the empty vector-infected cells. However, increased NGAL expressiondid not alter the sensitivity of the cells to the chemotherapeutic drug doxorubicin. Thus, although NGAL expression is often detected after chemotherapeutic drug treatment, it by itself, does not lead to doxorubicin resistance.

Original languageEnglish
Pages (from-to)1236-1245
Number of pages10
JournalOncotarget
Volume3
Issue number10
Publication statusPublished - 2012

Keywords

  • Doxorubicin
  • Drug resistance
  • Iron transport
  • Lcn2
  • Lipocalins
  • MMP-9
  • NGAL
  • Siderocalins

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Chappell, W. H., Abrams, S. L., Montalto, G., Cervello, M., Martelli, A. M., Candido, S., Libra, M., Polesel, J., Talamini, R., Arlinghaus, R., Steelman, L. S., & McCubrey, J. A. (2012). Effects of ectopic expression of NGAL on doxorubicin sensitivity. Oncotarget, 3(10), 1236-1245.