Src/STAT3-dependent heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to doxorubicin by promoting autophagy.
Bottom Line: In the present study, we found an induction of HO-1 expression in doxorubicin (DOX)-treated MDA-MB-231 human breast adenocarcinoma cells, which showed insensitivity to DOX treatment.Knockdown HO-1 expression dramatically upregulated the incidence of MDA-MB-231 cell death under DOX treatment, indicating that HO-1 functions as a critical contributor to drug resistance in MDA-MB-231 cells.Moreover, upregulation of HO-1 expression required the activation of both signal transducer and activator of transcription (STAT)3 and its upstream regulator, protein kinase Src.
Affiliation: Department of Stress Medicine, Beijing Institute of Basic Medical Sciences, Beijing, China.Show MeSH
Related in: MedlinePlus
Mentions: Both JAK2 and Src kinases are well-known cytoplasmic tyrosine kinases that are responsible for phosphorylating and activating STAT3.30,31 Therefore, to determine the upstream signal molecules leading to STAT3 activation in MDA-MB-231 cells under DOX exposure, we next detected the activation status of Src and JAK2 in the DOX-treated MDA-MB-231 and MDA-MB-453 cells. As shown in Figure5(a), after treatment with DOX, phosphorylation of Src was only significantly induced in MDA-MB-231 cells, but not in MDA-MB-453 cells. No signal of JAK2 activation was detected in either MDA-MB-231 or MDA-MB-453 cells under the same DOX exposure conditions (data not show).
Affiliation: Department of Stress Medicine, Beijing Institute of Basic Medical Sciences, Beijing, China.