Open AccessSynergistic repression of thyroid hyperplasia by cyclin C and Pten
Author(s) -
Jan Ježek,
Kun Wang,
Ruilan Yan,
Antonio Di Cristofano,
Katrina F. Cooper,
Randy Strich
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.230029
Subject(s) - pten , cancer research , biology , cyclin d , tumor suppressor gene , cyclin d1 , thyroid , oncogene , cyclin b , p14arf , carcinogenesis , pi3k/akt/mtor pathway , microbiology and biotechnology , cell cycle , endocrinology , cancer , signal transduction , genetics
The cyclin C-Cdk8 kinase has been identified as a tumor suppressor or oncogene depending on the cell type. The genomic locus encoding cyclin C (Ccnc) is often deleted in aggressive anaplastic thyroid tumors. To test a potential tumor suppressor role for cyclin C, Ccnc alone, or in combination with a previously described thyroid tumor suppressor Pten, was deleted late in thyroid development. Although mice harboring individual Pten or Ccnc deletions exhibited modest thyroid hyperplasia, the double mutant demonstrated dramatic thyroid expansion resulting in animal death by 22 weeks. Further analysis revealed that Ccncthyr−/−tissues exhibited a reduction in Signal Transducer and Activator of Transcription 3 (Stat3) phosphorylation at Ser727. Further analysis uncovered a post-transcriptional requirement of both Pten and cyclin C in maintaining the levels of the p21 and p53 tumor suppressors in thyroid tissue. In conclusion, these data reveal the first tumor suppressor role for cyclin C in a solid tumor model. In addition, this study uncovers new synergistic activities of Pten and cyclin C to promote quiescence through maintenance of p21 and p53.