PMID- 14508520
OWN - NLM
STAT- MEDLINE
DCOM- 20031023
LR  - 20220317
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 41
DP  - 2003 Sep 25
TI  - Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 
      gene expression.
PG  - 6395-407
AB  - 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.
FAU - Lynch, John
AU  - Lynch J
AD  - Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA. lynchj@mail.med.upenn.edu
FAU - Keller, Matthew
AU  - Keller M
FAU - Guo, Rong-Jun
AU  - Guo RJ
FAU - Yang, Donald
AU  - Yang D
FAU - Traber, Peter
AU  - Traber P
LA  - eng
GR  - DK02695-02/DK/NIDDK NIH HHS/United States
GR  - P01-DK49210/DK/NIDDK NIH HHS/United States
GR  - P30-DK50306/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CDX1 protein, human)
RN  - 0 (Cdx1 protein, mouse)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (RNA, Messenger)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Animals
MH  - Cell Cycle/physiology
MH  - Cell Division/*physiology
MH  - Colonic Neoplasms/*metabolism
MH  - Cyclin D1/biosynthesis/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/*metabolism
MH  - Humans
MH  - Mice
MH  - RNA, Messenger/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2003/09/26 05:00
MHDA- 2003/10/24 05:00
CRDT- 2003/09/26 05:00
PHST- 2003/09/26 05:00 [pubmed]
PHST- 2003/10/24 05:00 [medline]
PHST- 2003/09/26 05:00 [entrez]
AID - 1206770 [pii]
AID - 10.1038/sj.onc.1206770 [doi]
PST - ppublish
SO  - Oncogene. 2003 Sep 25;22(41):6395-407. doi: 10.1038/sj.onc.1206770.