CCNB1 affects cavernous sinus invasion in pituitary adenomas through the epithelial-mesenchymal transition

J Transl Med. 2019 Oct 4;17(1):336. doi: 10.1186/s12967-019-2088-8.

Abstract

Background: To investigate the relationship between cyclin B1 (CCNB1) gene expression and cavernous sinus invasion in pituitary adenomas.

Methods: Twenty-four pituitary adenoma tissue samples were examined by RT-qPCR and Western blot to assess the mRNA expression levels and protein levels of CCNB1, E-cadherin and N-cadherin. Correlation analyses between the expression levels of E-cadherin, N-cadherin and CCNB1 were performed. After lentivirus-mediated knockdown of CCNB1 in rat pituitary adenoma cell lines (GH3 and GT1-1), cell function changes were studied. The relationship between CCNB1 and epithelial-mesenchymal transition (EMT) was further verified by animal experiments.

Results: CCNB1 and N-cadherin gene expression were significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas. Conversely, E-cadherin expression in the invasive pituitary adenomas was significantly lower. CCNB1 gene expression was downregulated in the GH3 and GT1-1 pituitary adenoma cell lines; N-cadherin expression was also decreased, but E-cadherin expression was increased. These results were confirmed in vivo. After downregulation of CCNB1, cell invasion and migration was significantly reduced in Transwell experiments.

Conclusion: High CCNB1 expression in pituitary adenoma affects cavernous sinus invasion through EMT.

Keywords: CCNB1 gene; Cavernous sinus invasion; E-Cadherin; Epithelial–mesenchymal transition; N-Cadherin; Pituitary adenoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Adult
  • Aged
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cavernous Sinus / diagnostic imaging
  • Cavernous Sinus / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cyclin B1 / metabolism*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lentivirus / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Pituitary Neoplasms / diagnostic imaging
  • Pituitary Neoplasms / genetics
  • Pituitary Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats

Substances

  • CCNB1 protein, human
  • Cadherins
  • Ccnb1 protein, rat
  • Cyclin B1
  • RNA, Messenger