title: AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel.
abstract: Paclitaxel (PTX) has shown encouraging activity in the treatment of advanced gastric cancer (GC). However, the fact that more than half of GC patients respond poorly to PTX-based chemotherapies demonstrates the urgent need for biomarkers of PTX sensitivity in GC patients. In the present work, three GC cell lines (BGC-823, HGC-27 and NCI-N87) with different sensitivities to PTX were subjected to DNA microarray analysis. The significantly differentially expressed genes and microRNAs (miRs) were identified and pathway signatures for PTX sensitivity were proposed. Ingenuity Pathway Analysis results showed that the differentially expressed genes were mainly enriched in the ErbB signaling pathway and other pathways. Additionally, the AKT/ERK signaling pathway, which is the pathway downstream of ErbB, was predicted to be active in PTX-resistant GC cell lines. ErbB3 overexpression and AKT/ERK activation in PTX-resistant cell lines were validated, respectively, by quantitative PCR and immunoblotting. Furthermore, 10 miRs were dramatically differently expressed in the three GC cell lines, and a miR-gene network was constructed from these data. Our work uncovered a reliable signature for PTX sensitivity in GC and potential therapeutic targets for GC treatments.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University Shanghai 200040, China ; Department of General Surgery, Renhe Hospital Baoshan District, Shanghai 20043, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Renhe Hospital Baoshan District, Shanghai 20043, China.
authors.forename: Xue-Qian
authors.initials: XQ
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Renhe Hospital Baoshan District, Shanghai 20043, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Li
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017211:Treatment Failure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018739:Oncogene Proteins v-erbB; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D017239:Paclitaxel
keywords: AKT signaling; DNA microarray; ERK signaling; ErbB signaling; Gastric cancer; microRNA; paclitaxel