Oncotarget

Research Papers:

Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity.

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

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Oncotarget. 2012; 3:1236-1245. https://doi.org/10.18632/oncotarget.691

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Abstract

William H. Chappell1, Stephen L. Abrams1, Giuseppe Montalto2,3, Melchiorre Cervello3, Alberto M. Martelli4,5, Saverio Candido6, Massimo Libra6, Jerry Polesel7, Renato Talamini7, Ralph Arlinghaus8, Linda S. Steelman1 and James A. McCubrey1

1 Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA 27834

2 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy

3 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy

4 Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy

5 Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute, Bologna, Italy

6 Department of Bio-Medical Sciences, University of Catania, Catania, Italy

7 Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.

8 Department of Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX

Correspondence:

James A. McCubrey, email:

Keywords: NGAL, Lcn2, Doxorubicin, lipocalins, siderocalins, iron transport, MMP-9, drug resistance

Received: October 01, 2012, Accepted: October 18, 2012, Published: October 20, 2012

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 expression did 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.


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