title: Effects of ectopic expression of NGAL on doxorubicin sensitivity.
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.
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Chappell
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Abrams
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Saverio
authors.initials: S
authors.lastname: Candido
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Ralph
authors.initials: R
authors.lastname: Arlinghaus
authors.forename: Linda S
authors.initials: LS
authors.lastname: Steelman
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000209:Acute-Phase Proteins; D000903:Antibiotics, Antineoplastic; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D004317:Doxorubicin