PMID- 10201372
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20101118
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6726
DP  - 1999 Apr 1
TI  - Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
PG  - 422-6
AB  - Mutations in the adenomatous polyposis coli (APC) tumour-suppressor gene occur in
      most human colon cancers. Loss of functional APC protein results in the
      accumulation of beta-catenin. Mutant forms of beta-catenin have been discovered
      in colon cancers that retain wild-type APC genes, and also in melanomas,
      medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas. The 
      accumulation of beta-catenin activates genes that are responsive to transcription
      factors of the TCF/LEF family, with which beta-catenin interacts. Here we show
      that beta-catenin activates transcription from the cyclin D1 promoter, and that
      sequences within the promoter that are related to consensus TCF/LEF-binding sites
      are necessary for activation. The oncoprotein p21ras further activates
      transcription of the cyclin D1 gene, through sites within the promoter that bind 
      the transcriptional regulators Ets or CREB. Cells expressing mutant beta-catenin 
      produce high levels of cyclin D1 messenger RNA and protein constitutively.
      Furthermore, expression of a dominant-negative form of TCF in colon-cancer cells 
      strongly inhibits expression of cyclin D1 without affecting expression of cyclin 
      D2, cyclin E, or cyclin-dependent kinases 2, 4 or 6. This dominant-negative TCF
      causes cells to arrest in the G1 phase of the cell cycle; this phenotype can be
      rescued by expression of cyclin D1 under the cytomegalovirus promoter. Abnormal
      levels of beta-catenin may therefore contribute to neoplastic transformation by
      causing accumulation of cyclin D1.
FAU - Tetsu, O
AU  - Tetsu O
AD  - University of California, San Francisco, School of Medicine, Cancer Research
      Institute, 94143-0128, USA.
FAU - McCormick, F
AU  - McCormick F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Binding Sites
MH  - Blotting, Western
MH  - Cell Division/genetics
MH  - Colonic Neoplasms/*genetics
MH  - Consensus Sequence
MH  - Cyclin D1/*genetics
MH  - Cytoskeletal Proteins/genetics/*physiology
MH  - G1 Phase
MH  - *Gene Expression Regulation, Neoplastic
MH  - HeLa Cells
MH  - Humans
MH  - Luciferases/genetics
MH  - Mutagenesis, Site-Directed
MH  - Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TCF Transcription Factors
MH  - *Trans-Activators
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - beta Catenin
MH  - ras Proteins/physiology
EDAT- 1999/04/14 02:03
MHDA- 2001/03/23 10:01
CRDT- 1999/04/14 02:03
PHST- 1999/04/14 02:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/14 02:03 [entrez]
AID - 10.1038/18884 [doi]
PST - ppublish
SO  - Nature. 1999 Apr 1;398(6726):422-6. doi: 10.1038/18884.