Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis.
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.
Tatsuka
Masaaki
M
Department of Regulatory Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan.
Sato
Sunao
S
Kitajima
Shojiro
S
Suto
Shiho
S
Kawai
Hidehiko
H
Miyauchi
Mutsumi
M
Ogawa
Ikuko
I
Maeda
Masayo
M
Ota
Takahide
T
Takata
Takashi
T
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
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