Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Stephen L. Abrams (Creator)
Ralph Arlinghaus (Creator)
Saverio Candido (Creator)
Melchiorre Cervello (Creator)
William H. Chappell (Creator)
Massimo Libra (Creator)
Alberto M. Martelli (Creator)
James A. McCubrey (Creator)
Giuseppe Montalto (Creator)
Jerry Polesel (Creator)
Linda S. Steelman (Creator)
Renato Talamini (Creator)
Institution
East Carolina University (ECU )
Web Site: http://www.ecu.edu/lib/

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.; tool kit for event planners

Additional Information

Publication
Other
Oncotarget; 3:10 p. 1236-1245
Language: English
Date: 2012
Keywords
siderocalins, Lcn2, drug resistance, lipocalins, NGAL, iron transport, MMP-9, Doxorubicin

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Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivityhttp://hdl.handle.net/10342/5663The described resource references, cites, or otherwise points to the related resource.