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Tytuł:
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Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.
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Autorzy:
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Yaguchi K; Graduate School of Life Science, Hokkaido University, Japan.
Yamamoto T; Graduate School of Life Science, Hokkaido University, Japan.
Shimada M; Graduate School of Life Science, Hokkaido University, Japan.
Sugimoto R; Graduate School of Life Science, Hokkaido University, Japan.
Nakamura K; Graduate School of Life Science, Hokkaido University, Japan.
Ayabe T; Graduate School of Life Science, Hokkaido University, Japan; Faculty of Advanced Life Science, Hokkaido University, Japan.
Uehara R; Graduate School of Life Science, Hokkaido University, Japan; Faculty of Advanced Life Science, Hokkaido University, Japan. Electronic address: .
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Źródło:
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Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Sep 26; Vol. 504 (1), pp. 231-237. Date of Electronic Publication: 2018 Sep 05.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
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MeSH Terms:
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Gene Expression Regulation*
Haploidy*
Ploidies*
Cyclin D2/*metabolism
Cyclin-Dependent Kinase 4/*metabolism
Cyclin-Dependent Kinase 6/*metabolism
Cell Line ; Cell Proliferation ; Humans ; Phosphorylation ; RNA Interference
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Contributed Indexing:
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Keywords: Cyclin D; Ploidy
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Substance Nomenclature:
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0 (CCND2 protein, human)
0 (Cyclin D2)
EC 2.7.11.22 (CDK4 protein, human)
EC 2.7.11.22 (CDK6 protein, human)
EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
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Entry Date(s):
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Date Created: 20180909 Date Completed: 20190325 Latest Revision: 20190325
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Update Code:
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20240104
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DOI:
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10.1016/j.bbrc.2018.08.160
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PMID:
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30193733
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Near-haploidy is observed in certain cancer types, but ploidy-dependent alterations in gene regulation in the haploid state remain elusive. Here, by comparative transcriptome analysis between human isogenic haploid and diploid cell lines, we found lowering of cyclin D2 level in haploids. Acute genome duplication in haploids restored cyclin D2 expression to diploid level, indicating that the regulation of cyclin D2 expression is directly linked to ploidy. Downstream pathways of cyclin D2, such as Rb phosphorylation and p27 sequestration remained intact in haploids, suggesting that they adapt to lowered cyclin D level. Interestingly, however, haploid cells were more susceptible to cdk4/6 inhibition compared to diploids. Our finding indicates feasibility of selective growth suppression of haploid cells based on ploidy-linked gene regulation.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
