The conserved protective cyclic AMP-phosphodiesterase function PDE4B is expressed in the adenoma and adjacent normal colonic epithelium of mammals and silenced in colorectal cancer.
PLoS Genet
; 14(9): e1007611, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30188895
ABSTRACT
Conservation over three mammalian genera-the mouse, rat, and human-has been found for a subset of the transcripts whose level differs between the adenoma and normal epithelium of the colon. Pde4b is one of the triply conserved transcripts whose level is enhanced both in the colonic adenoma and in the normal colonic epithelium, especially adjacent to adenomas. It encodes the phosphodiesterase PDE4B, specific for cAMP. Loss of PDE4B function in the ApcMin/+ mouse leads to a significant increase in the number of colonic adenomas. Similarly, Pde4b-deficient ApcMin/+ mice are hypersensitive to treatment by the inflammatory agent DSS, becoming moribund soon after treatment. These observations imply that the PDE4B function protects against ApcMin-induced adenomagenesis and inflammatory lethality. The paradoxical enhancement of the Pde4b transcript in the adenoma versus this inferred protective function of PDE4B can be rationalized by a feedback model in which PDE4B is first activated by early oncogenic stress involving cAMP and then, as reported for frank human colon cancer, inactivated by epigenetic silencing.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Doenças Inflamatórias Intestinais
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Adenoma
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AMP Cíclico
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos