Kif14 overexpression accelerates murine retinoblastoma development.
The mitotic kinesin KIF14 has an essential role in the recruitment of proteins required for the final stages of cytokinesis. Genomic gain and/or overexpression of KIF14 has been documented in retinoblastoma and a number of other cancers, such as breast, lung and ovarian carcinomas, strongly suggesting its role as an oncogene. Despite evidence of oncogenic properties in vitro and in xenografts, Kif14's role in tumor progression has not previously been studied in a transgenic cancer model. Using a novel Kif14 overexpressing, simian virus 40 large T-antigen retinoblastoma (TAg-RB) double transgenic mouse model, we aimed to determine Kif14's role in promoting retinal tumor formation. Tumor initiation and development in double transgenics and control TAg-RB littermates were documented in vivo over a time course by optical coherence tomography, with subsequent ex vivo quantification of tumor burden. Kif14 overexpression led to an accelerated initiation of tumor formation in the TAg-RB model and a significantly decreased tumor doubling time (1.8 vs. 2.9 weeks). Moreover, overall percentage tumor burden was also increased by Kif14 overexpression. These data provide the first evidence that Kif14 can promote tumor formation in susceptible cells in vivo.
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.|Biomedical Science, University of Ulster, Coleraine, United Kingdom.
Michael
M
O'Hare
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.
Mehdi
M
Shadmand
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.|Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN.|Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Rania S
RS
Sulaiman
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.
Kamakshi
K
Sishtla
Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Toshiaki
T
Sakisaka
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.|Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.|Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Timothy W
0000-0002-1402-7875
TW
Corson
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis; D048708:Cell Growth Processes / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D016547:Kinesins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013539:Simian virus 40 / Q000276:immunology
D000957:Antigens, Viral, Tumor; C581966:Kif14 protein, mouse; D016547:Kinesins
kinesin; oncogene; optical coherence tomography; retinoblastoma; transgenic mouse