Neighbors' death is required for surviving human adenocarcinoma PC-9 cells in an early stage of gefitinib treatment.
Acquired drug resistance is a major problem in chemotherapy, and understanding of the mechanism, by which naïve cells defend themselves from drugs when the cells exposed to the drugs for the first time, may provide a solution of the problem. Gefitinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and used as an anticancer drug; however, gefitinib treatment may sometimes lead cancer cells gradually into a gefitinib-tolerance. Here we describe that human adenocarcinoma PC-9 cells even under the presence of gefitinib were able to survive by activating another signaling pathway involving fibroblast growth factor receptor (FGFR) and its signaling molecule, FGF2; and further suggest that the FGF2 for initiating the pathway might be supplied from neighboring cells which were killed by gefitinib, i.e., the survival might be founded on neighbors' sacrifice in an early stage of gefitinib treatment. Our findings suggested that whether cells had a chance to encounter to survival factors such as FGF2 soon after gefitinib treatment might be an important crossroads for the cells for survival and for gaining a gefitinib tolerance.
['Takahashi|Masaki|M|', 'Fukuoka|Masashi|M|', 'Yoshioka|Katsuji|K|', 'Hohjoh|Hirohiko|H|']
D000230:Adenocarcinoma D002289:Carcinoma, Non-Small-Cell Lung D016923:Cell Death D045744:Cell Line, Tumor D002470:Cell Survival D004305:Dose-Response Relationship, Drug D019008:Drug Resistance, Neoplasm D066246:ErbB Receptors D016222:Fibroblast Growth Factor 2 D000077156:Gefitinib D020869:Gene Expression Profiling D006801:Humans D008175:Lung Neoplasms D011799:Quinazolines D017468:Receptors, Fibroblast Growth Factor D015398:Signal Transduction D016896:Treatment Outcome
Gefitinib PC-9 cells Fibroblast growth factor receptor (FGFR) FGF2 Epidermal growth factor receptor (EGFR) Gefitinib resistance