Stromal iodothyronine deiodinase 2 (DIO2) promotes the growth of intestinal tumors in Apc^Δ716 mutant mice.

ABSTRACT: Iodothyronine deiodinase 2 (DIO2) converts the prohormone thyroxine (T4) to bioactive T3 in peripheral tissues and thereby regulates local thyroid hormone (TH) levels. Although epidemiologic studies suggest the contribution of TH to the progression of colorectal cancer (CRC), the role of DIO2 in CRC remains elusive. Here we show that Dio2 is highly expressed in intestinal polyps of Apc^Δ716 mice, a mouse model of familial adenomatous polyposis and early stage sporadic CRC. Laser capture microdissection and in situ hybridization analysis show almost exclusive expression of Dio2 in the stroma of Apc^Δ716 polyps in the proximity of the COX-2-positive areas. Treatment with iopanoic acid, a deiodinase inhibitor, or chemical thyroidectomy suppresses tumor formation in Apc

SUBMITTER: Kojima Y 

PROVIDER: S-EPMC6676103 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature