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KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors

Our group has previously demonstrated that pfetin, encoded by the KCTD12 gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of KCTD12 in GIST, in...

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Autores principales: Suehara, Yoshiyuki, Akaike, Keisuke, Mukaihara, Kenta, Kurisaki-Arakawa, Aiko, Kubota, Daisuke, Okubo, Taketo, Mitomi, Hiroyuki, Mitani, Keiko, Takahashi, Michiko, Toda-Ishii, Midori, Kim, Youngji, Tanabe, Yu, Takagi, Tatsuya, Hayashi, Takuo, Mogushi, Kaoru, Kaneko, Kazuo, Yao, Takashi, Saito, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007475/
https://www.ncbi.nlm.nih.gov/pubmed/29930747
http://dx.doi.org/10.18632/oncotarget.25469
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author Suehara, Yoshiyuki
Akaike, Keisuke
Mukaihara, Kenta
Kurisaki-Arakawa, Aiko
Kubota, Daisuke
Okubo, Taketo
Mitomi, Hiroyuki
Mitani, Keiko
Takahashi, Michiko
Toda-Ishii, Midori
Kim, Youngji
Tanabe, Yu
Takagi, Tatsuya
Hayashi, Takuo
Mogushi, Kaoru
Kaneko, Kazuo
Yao, Takashi
Saito, Tsuyoshi
author_facet Suehara, Yoshiyuki
Akaike, Keisuke
Mukaihara, Kenta
Kurisaki-Arakawa, Aiko
Kubota, Daisuke
Okubo, Taketo
Mitomi, Hiroyuki
Mitani, Keiko
Takahashi, Michiko
Toda-Ishii, Midori
Kim, Youngji
Tanabe, Yu
Takagi, Tatsuya
Hayashi, Takuo
Mogushi, Kaoru
Kaneko, Kazuo
Yao, Takashi
Saito, Tsuyoshi
author_sort Suehara, Yoshiyuki
collection PubMed
description Our group has previously demonstrated that pfetin, encoded by the KCTD12 gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of KCTD12 in GIST, in addition to a possible association between KCTD12 alterations and protein expression, we examined 76 patients with GISTs for KCTD12 mutations by PCR-direct sequence, and compared these results with clinicopathologic data. The function of pfetin in GIST progression was also revealed using GIST T1 cells. In this series, pfetin expression was not observed in 15 cases, and loss of pfetin expression was associated with higher mitotic rate (>5/50HPFs: p = 0.029). There was also a trend between presence of necrosis and loss of pfetin expression but this was not statistically significant (p = 0.09). KCTD12 mutations were frequently observed in 22 out of 76 GISTs (28.9%); however, they did not affect protein expression and were not associated with patients’ prognosis. KCTD12 in vitro knockdown resulted in the accelerated growth of GIST T1 cells, confirming that pfetin functions as a tumor suppressor. KIT knockdown significantly inhibited cellular growth and upregulated the expression of pfetin at both the mRNA and protein level. These findings suggest that GISTs with loss of pfetin expression has proliferative advantage and that higher pfetin expression in GISTs may be indicative of lower expression levels of KIT. This relationship confirms that pfetin is a useful prognostic marker in GISTs.
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spelling pubmed-60074752018-06-21 KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors Suehara, Yoshiyuki Akaike, Keisuke Mukaihara, Kenta Kurisaki-Arakawa, Aiko Kubota, Daisuke Okubo, Taketo Mitomi, Hiroyuki Mitani, Keiko Takahashi, Michiko Toda-Ishii, Midori Kim, Youngji Tanabe, Yu Takagi, Tatsuya Hayashi, Takuo Mogushi, Kaoru Kaneko, Kazuo Yao, Takashi Saito, Tsuyoshi Oncotarget Research Paper Our group has previously demonstrated that pfetin, encoded by the KCTD12 gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of KCTD12 in GIST, in addition to a possible association between KCTD12 alterations and protein expression, we examined 76 patients with GISTs for KCTD12 mutations by PCR-direct sequence, and compared these results with clinicopathologic data. The function of pfetin in GIST progression was also revealed using GIST T1 cells. In this series, pfetin expression was not observed in 15 cases, and loss of pfetin expression was associated with higher mitotic rate (>5/50HPFs: p = 0.029). There was also a trend between presence of necrosis and loss of pfetin expression but this was not statistically significant (p = 0.09). KCTD12 mutations were frequently observed in 22 out of 76 GISTs (28.9%); however, they did not affect protein expression and were not associated with patients’ prognosis. KCTD12 in vitro knockdown resulted in the accelerated growth of GIST T1 cells, confirming that pfetin functions as a tumor suppressor. KIT knockdown significantly inhibited cellular growth and upregulated the expression of pfetin at both the mRNA and protein level. These findings suggest that GISTs with loss of pfetin expression has proliferative advantage and that higher pfetin expression in GISTs may be indicative of lower expression levels of KIT. This relationship confirms that pfetin is a useful prognostic marker in GISTs. Impact Journals LLC 2018-06-05 /pmc/articles/PMC6007475/ /pubmed/29930747 http://dx.doi.org/10.18632/oncotarget.25469 Text en Copyright: © 2018 Suehara et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Suehara, Yoshiyuki
Akaike, Keisuke
Mukaihara, Kenta
Kurisaki-Arakawa, Aiko
Kubota, Daisuke
Okubo, Taketo
Mitomi, Hiroyuki
Mitani, Keiko
Takahashi, Michiko
Toda-Ishii, Midori
Kim, Youngji
Tanabe, Yu
Takagi, Tatsuya
Hayashi, Takuo
Mogushi, Kaoru
Kaneko, Kazuo
Yao, Takashi
Saito, Tsuyoshi
KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title_full KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title_fullStr KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title_full_unstemmed KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title_short KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors
title_sort kctd12 is negatively regulated by kit in gastrointestinal stromal tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007475/
https://www.ncbi.nlm.nih.gov/pubmed/29930747
http://dx.doi.org/10.18632/oncotarget.25469
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