title: IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model.
abstract: Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Yanhan
authors.initials: Y
authors.lastname: Jia
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qiao
authors.forename: Guijun
authors.initials: G
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D000068878:Trastuzumab; D015854:Up-Regulation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D000068878:Trastuzumab
keywords: Drug resistance; ErbB3/HER3; IGF-1R; Ovarian cancer; Trastuzumab