PMID- 10318916
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 10
DP  - 1999 May 11
TI  - The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway.
PG  - 5522-7
AB  - beta-Catenin plays a dual role in the cell: one in linking the cytoplasmic side
      of cadherin-mediated cell-cell contacts to the actin cytoskeleton and an
      additional role in signaling that involves transactivation in complex with
      transcription factors of the lymphoid enhancing factor (LEF-1) family. Elevated
      beta-catenin levels in colorectal cancer caused by mutations in beta-catenin or
      by the adenomatous polyposis coli molecule, which regulates beta-catenin
      degradation, result in the binding of beta-catenin to LEF-1 and increased
      transcriptional activation of mostly unknown target genes. Here, we show that the
      cyclin D1 gene is a direct target for transactivation by the beta-catenin/LEF-1
      pathway through a LEF-1 binding site in the cyclin D1 promoter. Inhibitors of
      beta-catenin activation, wild-type adenomatous polyposis coli, axin, and the
      cytoplasmic tail of cadherin suppressed cyclin D1 promoter activity in colon
      cancer cells. Cyclin D1 protein levels were induced by beta-catenin
      overexpression and reduced in cells overexpressing the cadherin cytoplasmic
      domain. Increased beta-catenin levels may thus promote neoplastic conversion by
      triggering cyclin D1 gene expression and, consequently, uncontrolled progression 
      into the cell cycle.
FAU - Shtutman, M
AU  - Shtutman M
AD  - Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 
      76100, Israel.
FAU - Zhurinsky, J
AU  - Zhurinsky J
FAU - Simcha, I
AU  - Simcha I
FAU - Albanese, C
AU  - Albanese C
FAU - D'Amico, M
AU  - D'Amico M
FAU - Pestell, R
AU  - Pestell R
FAU - Ben-Ze'ev, A
AU  - Ben-Ze'ev A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Axin Protein)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (LEF1 protein, human)
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein
MH  - Axin Protein
MH  - Binding Sites
MH  - Cadherins/metabolism
MH  - Colonic Neoplasms/genetics
MH  - Cyclin D1/*genetics/metabolism
MH  - Cytoskeletal Proteins/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Lymphoid Enhancer-Binding Factor 1
MH  - Promoter Regions, Genetic
MH  - Proteins
MH  - *Repressor Proteins
MH  - Signal Transduction
MH  - *Trans-Activators
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - beta Catenin
PMC - PMC21892
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1073/pnas.96.10.5522 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7. doi:
      10.1073/pnas.96.10.5522.