Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.
Biochem Biophys Res Commun
; 504(1): 231-237, 2018 09 26.
Article
em En
| MEDLINE
| ID: mdl-30193733
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ploidias
/
Regulação da Expressão Gênica
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Quinase 4 Dependente de Ciclina
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Quinase 6 Dependente de Ciclina
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Ciclina D2
/
Haploidia
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article