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. 2018 Sep 6;14(9):e1007611. doi: 10.1371/journal.pgen.1007611. eCollection 2018 Sep.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / genetics
  • Adenoma / mortality
  • Adenoma / pathology*
  • Adenomatous Polyposis Coli Protein / genetics
  • Animals
  • Colon / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Cyclic AMP / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Female
  • Gene Knockout Techniques
  • Humans
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / pathology*
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Rats
  • Tissue Array Analysis


  • Adenomatous Polyposis Coli Protein
  • adenomatous polyposis coli protein, mouse
  • Dextran Sulfate
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4B protein, human
  • PDE4B protein, mouse
  • PDE4B protein, rat