title: Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis.
abstract: Aurora kinases are known to play a key role in maintaining mitotic fidelity, and overexpression of aurora kinases has been noted in various tumors. Overexpression of aurora kinase activity is thought to promote cancer development through a loss of centrosome or chromosome number integrity. Here we observed augmentation of G12V-mutated HRAS-induced neoplastic transformation in BALB/c 3T3 A31-1-1 cells transfected with Aurora-A. Aurora-A-short hairpin RNA (shRNA) experiments showed that the expression level of Aurora-A determines susceptibility to transformation. Aurora-A gene amplification was noted in human patients with tongue or gingival squamous carcinoma (4/11). Amplification was observed even in pathologically normal epithelial tissue taken at sites distant from the tumors in two patients with tongue cancer. However, overexpression of Aurora-A mRNA was observed only within the tumors of all patients examined (11/11). Our data indicate that Aurora-A gene amplification and overexpression play a role in human carcinogenesis, largely due to the effect of Aurora-A on oncogenic cell growth, rather than a loss of maintenance of centrosomal or chromosomal integrity.
authors.affiliation: Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tatsuka
authors.forename: Sunao
authors.initials: S
authors.lastname: Sato
authors.forename: Shojiro
authors.initials: S
authors.lastname: Kitajima
authors.forename: Shiho
authors.initials: S
authors.lastname: Suto
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kawai
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogawa
authors.forename: Masayo
authors.initials: M
authors.lastname: Maeda
authors.forename: Takahide
authors.initials: T
authors.lastname: Ota
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D064127:Aurora Kinases; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology*; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005887:Gingival Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014062:Tongue Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D029867:Xenopus Proteins; D018631:ras Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D018631:ras Proteins