These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression.
    Author: Lynch J, Keller M, Guo RJ, Yang D, Traber P.
    Journal: Oncogene; 2003 Sep 25; 22(41):6395-407. PubMed ID: 14508520.
    Abstract:
    The transcription factor Cdx1 regulates intestine-specific gene expression and enterocyte differentiation. It has been hypothesized to play a role in regulating intestinal cell proliferation; however, the mechanism for this effect remains elusive. In a prior study, we demonstrated that Cdx1 expression reduced the proliferation of a nontransformed intestinal cell line. This study tests the hypothesis that Cdx1 expression inhibits colon cancer cell proliferation by reducing cyclin D1 gene expression. Cdx1 expression markedly reduced cancer cell proliferation and DNA synthesis and induced an accumulation of cells in G0/G1. A transcriptionally inactive Cdx1 mutant could not elicit this effect, suggesting that it required Cdx1 transcriptional activity. Cdx1 expression increased the hypophosphorylation of the retinoblastoma (pRb) and p130 proteins. Reductions in G1 cyclin-dependant kinase (cdk) activity accompanied this effect. Cyclin D1 mRNA and protein levels were diminished by Cdx1 expression. Restoration of cyclin D1 expression reversed the G0/G1 block and induced pRb hyperphosphorylation. Lastly, Cdx1 expression did not alter cyclin D1 mRNA stability but did reduce cyclin D1 promoter activity, suggesting that Cdx1 acts to diminish cyclin D1 gene transcription. We conclude that Cdx1 reduces the proliferation of human colon cancer cells by reducing cyclin D1 gene transcription.
    [Abstract] [Full Text] [Related] [New Search]