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The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells

OBJECTIVE: Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also...

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Autores principales: Thériault, Brigitte L, Cybulska, Paulina, Shaw, Patricia A, Gallie, Brenda L, Bernardini, Marcus Q
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302703/
https://www.ncbi.nlm.nih.gov/pubmed/25528264
http://dx.doi.org/10.1186/s13048-014-0123-1
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author Thériault, Brigitte L
Cybulska, Paulina
Shaw, Patricia A
Gallie, Brenda L
Bernardini, Marcus Q
author_facet Thériault, Brigitte L
Cybulska, Paulina
Shaw, Patricia A
Gallie, Brenda L
Bernardini, Marcus Q
author_sort Thériault, Brigitte L
collection PubMed
description OBJECTIVE: Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also controls the in vivo tumorigenicity of OvCa cell lines. In this study, we evaluate the potential of KIF14 as a therapeutic target through selective inhibition of KIF14 in primary high-grade serous patient-derived OvCa cells. METHODS: To assess the dependence of primary serous OvCa cultures on KIF14, protein levels in 11 prospective high grade serous ovarian cancer samples were increased (KIF14 overexpression by transfection) or decreased (anti-KIF14 shRNA) in vitro, and proliferative capacity, anchorage independence and xenograft growth were assessed. RESULTS: Seven of eleven samples demonstrated increased/decreased in vitro proliferation in response to KIF14 overexpression/knockdown, respectively. When examining in vitro tumorigenicity (colony formation) and in vivo growth (subcutaneous xenografts) in response to KIF14 manipulation, none of the samples demonstrated growth in soft agar (11 samples), or xenograft growth (4 samples). CONCLUSIONS: Although primary high-grade serous OvCa cells may depend on KIF14 for in vitro proliferation we were unable to demonstrate a role for KIF14 on tumorigenicity or develop an in vivo model for assessment. We have, however developed an effective in vitro method to evaluate the effect of target gene manipulation on the proliferative capacity of primary OvCa cultures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0123-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-43027032015-01-23 The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells Thériault, Brigitte L Cybulska, Paulina Shaw, Patricia A Gallie, Brenda L Bernardini, Marcus Q J Ovarian Res Research OBJECTIVE: Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also controls the in vivo tumorigenicity of OvCa cell lines. In this study, we evaluate the potential of KIF14 as a therapeutic target through selective inhibition of KIF14 in primary high-grade serous patient-derived OvCa cells. METHODS: To assess the dependence of primary serous OvCa cultures on KIF14, protein levels in 11 prospective high grade serous ovarian cancer samples were increased (KIF14 overexpression by transfection) or decreased (anti-KIF14 shRNA) in vitro, and proliferative capacity, anchorage independence and xenograft growth were assessed. RESULTS: Seven of eleven samples demonstrated increased/decreased in vitro proliferation in response to KIF14 overexpression/knockdown, respectively. When examining in vitro tumorigenicity (colony formation) and in vivo growth (subcutaneous xenografts) in response to KIF14 manipulation, none of the samples demonstrated growth in soft agar (11 samples), or xenograft growth (4 samples). CONCLUSIONS: Although primary high-grade serous OvCa cells may depend on KIF14 for in vitro proliferation we were unable to demonstrate a role for KIF14 on tumorigenicity or develop an in vivo model for assessment. We have, however developed an effective in vitro method to evaluate the effect of target gene manipulation on the proliferative capacity of primary OvCa cultures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0123-1) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-21 /pmc/articles/PMC4302703/ /pubmed/25528264 http://dx.doi.org/10.1186/s13048-014-0123-1 Text en © Theriault et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Thériault, Brigitte L
Cybulska, Paulina
Shaw, Patricia A
Gallie, Brenda L
Bernardini, Marcus Q
The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title_full The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title_fullStr The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title_full_unstemmed The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title_short The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
title_sort role of kif14 in patient-derived primary cultures of high-grade serous ovarian cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302703/
https://www.ncbi.nlm.nih.gov/pubmed/25528264
http://dx.doi.org/10.1186/s13048-014-0123-1
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