Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

Kamakshi Sishtla, Natalie Pitt, Mehdi Shadmand, Michael N. O’Hare, Rania S. Sulaiman, Anthony L. Sinn, Keith Condon, Karen Pollok, George Sandusky, Timothy Corson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number16152
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Kinesin
Transgenic Mice
Neoplasms
Lymphoma
Breast
Retinoblastoma
B-Cell Lymphoma
Growth
Tumor Burden
Transgenes
Heterografts
Non-Hodgkin's Lymphoma
Lenses
Prostate
Cause of Death
Epithelial Cells
Genotype
Weights and Measures
Liver
Incidence

ASJC Scopus subject areas

  • General

Cite this

Sishtla, K., Pitt, N., Shadmand, M., O’Hare, M. N., Sulaiman, R. S., Sinn, A. L., ... Corson, T. (2018). Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14. Scientific Reports, 8(1), [16152]. https://doi.org/10.1038/s41598-018-34603-4

Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14. / Sishtla, Kamakshi; Pitt, Natalie; Shadmand, Mehdi; O’Hare, Michael N.; Sulaiman, Rania S.; Sinn, Anthony L.; Condon, Keith; Pollok, Karen; Sandusky, George; Corson, Timothy.

In: Scientific Reports, Vol. 8, No. 1, 16152, 01.12.2018.

Research output: Contribution to journalArticle

Sishtla K, Pitt N, Shadmand M, O’Hare MN, Sulaiman RS, Sinn AL et al. Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14. Scientific Reports. 2018 Dec 1;8(1). 16152. https://doi.org/10.1038/s41598-018-34603-4
Sishtla, Kamakshi ; Pitt, Natalie ; Shadmand, Mehdi ; O’Hare, Michael N. ; Sulaiman, Rania S. ; Sinn, Anthony L. ; Condon, Keith ; Pollok, Karen ; Sandusky, George ; Corson, Timothy. / Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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