Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity
Chappell, William H.; Abrams, Stephen L.; Montalto, Giuseppe; Cervello, Melchiorre; Martelli, Alberto M.; Candido, Saverio; Libra, Massimo; Polesel, Jerry; Talamini, Renato; Arlinghaus, Ralph; Steelman, Linda S.; McCubrey, James A.
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.
Chappell, William H., & Abrams, Stephen L., & Montalto, Giuseppe, & Cervello, Melchiorre, & Martelli, Alberto M., & Candido, Saverio, & Libra, Massimo, & Polesel, Jerry, & Talamini, Renato, & Arlinghaus, Ralph, & Steelman, Linda S., & McCubrey, James A.. (October 2012). Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity. Oncotarget, 3(10), 1236- 1245. Retrieved from http://hdl.handle.net/10342/5663
Chappell, William H., and Abrams, Stephen L., and Montalto, Giuseppe, and Cervello, Melchiorre, and Martelli, Alberto M., and Candido, Saverio, and Libra, Massimo, and Polesel, Jerry, and Talamini, Renato, and Arlinghaus, Ralph, and Steelman, Linda S., and McCubrey, James A.. "Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity". Oncotarget. 3:10. (1236-1245), October 2012. June 21, 2018. http://hdl.handle.net/10342/5663.
Chappell, William H. and Abrams, Stephen L. and Montalto, Giuseppe and Cervello, Melchiorre and Martelli, Alberto M. and Candido, Saverio and Libra, Massimo and Polesel, Jerry and Talamini, Renato and Arlinghaus, Ralph and Steelman, Linda S. and McCubrey, James A., "Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity," Oncotarget 3, no. 10 (October 2012), http://hdl.handle.net/10342/5663 (accessed June 21, 2018).
Chappell, William H., Abrams, Stephen L., Montalto, Giuseppe, Cervello, Melchiorre, Martelli, Alberto M., Candido, Saverio, Libra, Massimo, Polesel, Jerry, Talamini, Renato, Arlinghaus, Ralph, Steelman, Linda S., McCubrey, James A.. Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity. Oncotarget. October 2012; 3(10): 1236-1245. http://hdl.handle.net/10342/5663. Accessed June 21, 2018.