title: Establishment and characterization of a novel uterine carcinosarcoma cell line, TU-ECS-1, with mutations of TP53 and KRAS.
abstract: A new human uterine carcinosarcoma (UCS) cell line, TU-ECS-1, was established and characterized. The morphological appearance of the cultured cells was an insular of epithelial-like cells arranged in the form of a jigsaw puzzle and mesenchymal-like cells with a spindle-shaped or fibroblast-like morphology. A relatively high proliferation rate was observed with a doubling time of 18.2 h. The chromosome number ranged from 44 to 49 and had an extra chromosome 12 (trisomy 12). The respective half-maximal inhibitory concentrations of cisplatin, paclitaxel, and doxorubicin were 2.9 µM, 154 nM, and 219 ng/mL, respectively. Mutational analysis revealed that TU-ECS-1 cells have mutations of TP53 in exons 4, 6, and 8 and of KRAS at codon 12 (G12D) in exon 2, which is a mutation hot spot on this gene. Western blot analysis showed that p53 protein was overexpressed in TU-ECS-1 cells. Immunostaining of the cultured cells and in vivo tumors showed that the TU-ECS-1 cells and xenografts were positive for epithelial marker cytokeratin AE1/3 and mesenchymal marker vimentin. These results suggested that TU-ECS-1 cells might have both epithelial and mesenchymal characteristics. This cell line may be useful to study the carcinogenesis of UCS and contribute to the development of novel treatment strategies.
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan. itamochi@iwate-med.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.|Department of Pathology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fukagawa
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-8504, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Oumi
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-8504, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oishi
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-8504, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002296:Carcinosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D009154:Mutation; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
chemical_list: C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Establishment; KRAS; Molecular-targeted therapy; TP53; Uterine carcinosarcoma