Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

Abstract The KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, l...

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Autores principales:	Kamakshi Sishtla, Natalie Pitt, Mehdi Shadmand, Michael N. O’Hare, Rania S. Sulaiman, Anthony L. Sinn, Keith Condon, Karen E. Pollok, George E. Sandusky, Timothy W. Corson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Mitotic Kinesin Fatal Lymphoma KIF Expression Protein Regulator Of Cytokinesis 1 (PRC1) Citron Kinase Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9991ce83d254336892512c975a7ea45
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spelling	oai:doaj.org-article:c9991ce83d254336892512c975a7ea452021-12-02T15:08:54ZObservations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif1410.1038/s41598-018-34603-42045-2322https://doaj.org/article/c9991ce83d254336892512c975a7ea452018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34603-4https://doaj.org/toc/2045-2322Abstract The KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, liver, ovarian, breast, prostate, and other tumour cells and xenografts. However, the tumour-initiating effects of Kif14 overexpression have not been studied. We aged a cohort of Kif14-overexpressing transgenic mice and wild-type littermates and documented survival, cause of death, and tumour burden. The Kif14 transgene was expressed in all tissues examined, and was associated with increased proliferation marker expression. Neither mouse weights nor overall survival differed between genotypes. However, Kif14 transgenic mice showed a higher incidence of fatal lymphomas (73 vs. 50%, p = 0.03, Fisher’s exact test), primarily follicular and diffuse B-cell lymphomas. Non-tumour findings included a bilateral ballooning degeneration of lens in 12% of Kif14 transgenic mice but no wild-type mice (p = 0.02). Overall, this work reveals a novel association of Kif14 overexpression with lymphoma but suggests that Kif14 does not have as prominent a role in initiating cancer in other cell types as it does in accelerating tumour development in response to other oncogenic insults.Kamakshi SishtlaNatalie PittMehdi ShadmandMichael N. O’HareRania S. SulaimanAnthony L. SinnKeith CondonKaren E. PollokGeorge E. SanduskyTimothy W. CorsonNature PortfolioarticleMitotic KinesinFatal LymphomaKIF ExpressionProtein Regulator Of Cytokinesis 1 (PRC1)Citron KinaseMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mitotic Kinesin Fatal Lymphoma KIF Expression Protein Regulator Of Cytokinesis 1 (PRC1) Citron Kinase Medicine R Science Q
spellingShingle	Mitotic Kinesin Fatal Lymphoma KIF Expression Protein Regulator Of Cytokinesis 1 (PRC1) Citron Kinase Medicine R Science Q Kamakshi Sishtla Natalie Pitt Mehdi Shadmand Michael N. O’Hare Rania S. Sulaiman Anthony L. Sinn Keith Condon Karen E. Pollok George E. Sandusky Timothy W. Corson Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
description	Abstract The KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, liver, ovarian, breast, prostate, and other tumour cells and xenografts. However, the tumour-initiating effects of Kif14 overexpression have not been studied. We aged a cohort of Kif14-overexpressing transgenic mice and wild-type littermates and documented survival, cause of death, and tumour burden. The Kif14 transgene was expressed in all tissues examined, and was associated with increased proliferation marker expression. Neither mouse weights nor overall survival differed between genotypes. However, Kif14 transgenic mice showed a higher incidence of fatal lymphomas (73 vs. 50%, p = 0.03, Fisher’s exact test), primarily follicular and diffuse B-cell lymphomas. Non-tumour findings included a bilateral ballooning degeneration of lens in 12% of Kif14 transgenic mice but no wild-type mice (p = 0.02). Overall, this work reveals a novel association of Kif14 overexpression with lymphoma but suggests that Kif14 does not have as prominent a role in initiating cancer in other cell types as it does in accelerating tumour development in response to other oncogenic insults.
format	article
author	Kamakshi Sishtla Natalie Pitt Mehdi Shadmand Michael N. O’Hare Rania S. Sulaiman Anthony L. Sinn Keith Condon Karen E. Pollok George E. Sandusky Timothy W. Corson
author_facet	Kamakshi Sishtla Natalie Pitt Mehdi Shadmand Michael N. O’Hare Rania S. Sulaiman Anthony L. Sinn Keith Condon Karen E. Pollok George E. Sandusky Timothy W. Corson
author_sort	Kamakshi Sishtla
title	Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
title_short	Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
title_full	Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
title_fullStr	Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
title_full_unstemmed	Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14
title_sort	observations on spontaneous tumor formation in mice overexpressing mitotic kinesin kif14
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c9991ce83d254336892512c975a7ea45
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Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

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