Synergistic repression of thyroid hyperplasia by cyclin C and Pten

Jan Jezek, Kun Wang, Ruilan Yan, Antonio Di Cristofano, Katrina F. Cooper, Randy Strich

Research output: Contribution to journalArticle

Abstract

The cyclin C-Cdk8 kinase has been identified as both a tumor suppressor and an oncogene depending on the cell type. The genomic locus encoding cyclin C (Ccnc) is often deleted in aggressive anaplastic thyroid tumors. To test for a potential tumor suppressor role for cyclin C, Ccnc alone, or Ccnc 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 (also known as CDKN1A and TP53, respectively) 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.

Original languageEnglish (US)
JournalJournal of cell science
Volume132
Issue number16
DOIs
StatePublished - Aug 15 2019

Fingerprint

Cyclin C
Hyperplasia
Thyroid Gland
Neoplasms
STAT3 Transcription Factor
Oncogenes
Phosphotransferases

Keywords

  • Mouse knockout
  • p21
  • p53
  • Thyroid cancer

ASJC Scopus subject areas

  • Cell Biology

Cite this

Synergistic repression of thyroid hyperplasia by cyclin C and Pten. / Jezek, Jan; Wang, Kun; Yan, Ruilan; Di Cristofano, Antonio; Cooper, Katrina F.; Strich, Randy.

In: Journal of cell science, Vol. 132, No. 16, 15.08.2019.

Research output: Contribution to journalArticle

Jezek, Jan ; Wang, Kun ; Yan, Ruilan ; Di Cristofano, Antonio ; Cooper, Katrina F. ; Strich, Randy. / Synergistic repression of thyroid hyperplasia by cyclin C and Pten. In: Journal of cell science. 2019 ; Vol. 132, No. 16.
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