Abstract 2814: Effect of kif14 overexpression on tumor formation in mice in a lifespan study

Abstract

Abstract KIF14 is a mitotic kinesin and microtubule-associated molecular motor that plays an essential role in the last stages of cytokinesis. In multiple cancer types, KIF14, overexpression in tumors correlates with stage, aggressiveness, and poor patient outcomes. There is considerable interest in KIF14 as a possible oncogene, since the KIF14 locus is in a common region of genomic gain in multiple cancers. In this study, wild type BDF-1 mice and a strain constitutively overexpressing Kif14, known as Kif14-Tg mice, were evaluated at the end of their natural lifespan, specifically for the occurrence of tumors. There were approximately fifty mice per genotype, and eighty of these mice have died. These mice were necropsied and the following tissues were collected: kidney, liver, lung, spleen, seminal vesicles, ovary, mammary gland, bone marrow, pituitary gland, eye, and brain. Any gross nodules were also collected. These tissues were then fixed in 10% neutral buffered formalin, processed, sectioned, and stained with hematoxylin and eosin. Although there was no significant difference in mouse weights through the lifespan or in the survival curve between the Kif14-Tg and their wild type littermates, a significant increase in follicular lymphoma and diffuse large B cell lymphoma was seen in Kif14-Tg mice compared to the wild type mice. Thirty-three mice developed either a follicular lymphoma or a diffuse large B cell lymphoma, and twenty-four of those mice were Kif14-Tg mice. These were the two most common tumors in Kif14-Tg mice. Other lesions and tumors that were seen in both strains included thymic lymphoma, sarcomas, myeloid dysplasia, and other carcinomas. Nontumorous lesions were seen in both strains of mice including hydronephrosis and telangiectasia in multiple organs. Ballooning degeneration of the lens of the eyes was observed in five mice from the strain Kif14-Tg. Our finding of increased follicular lymphoma and diffuse large B cell lymphoma proves the first evidence that Kif14 can promote tumor formation in a wild-type background. This is the first evidence that Kif14 may have a role in lymphoma, but complements our earlier finding that Kif14 overexpression can accelerate tumor formation in a mouse model of retinoblastoma. Together, these outcomes further support Kif14’s potential as an oncogene. Citation Format: Natalie Pitt, Kamakshi Sishtla, Mehdi Shadmand, Rania Sulaiman, Anthony L. Sinn, Keith Condon, George E. Sandusky, Timothy W. Corson. Effect of kif14 overexpression on tumor formation in mice in a lifespan study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2814. doi:10.1158/1538-7445.AM2017-2814