1: Nat Genet. 2001 May;28(1):53-7. 

Comment in:
    Nat Genet. 2001 May;28(1):3-4.

Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively
expressed in colon cancer.

Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J,
Holcombe RF, Waterman ML.

Microbiology and Molecular Genetics Department, University of California,
Irvine, Irvine, California, USA.

Constitutive activation of the Wnt signaling pathway is a root cause of many
colon cancers. Activation of this pathway is caused by genetic mutations that
stabilize the beta-catenin protein, allowing it to accumulate in the nucleus and
form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell
factor (TCF1, TCF3, TCF4) family of transcription factors (referred to
collectively as LEF/TCFs) to activate transcription of target genes. Target
genes such as MYC, CCND1, MMP7 and TCF7 (refs. 5-9) are normally expressed in
colon tissue, so it has been proposed that abnormal expression levels or
patterns imposed by beta-catenin/TCF complexes have a role in tumor progression.
We report here that LEF1 is a new type of target gene ectopically activated in
colon cancer. The pattern of this ectopic expression is unusual because it
derives from selective activation of a promoter for a full-length LEF1 isoform
that binds beta-catenin, but not a second, intronic promoter that drives
expression of a dominant-negative isoform. beta-catenin/TCF complexes can
activate the promoter for full-length LEF1, indicating that in cancer high
levels of these complexes misregulate transcription to favor a positive feedback
loop for Wnt signaling by inducing selective expression of full-length,
beta-catenin-sensitive forms of LEF/TCFs.

PMID: 11326276 [PubMed - indexed for MEDLINE]


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2: Cell Immunol. 1996 Jul 10;171(1):41-7. 

Development and characterization of v-myc/v-raf-transformed murine fetal
thymocyte cell lines.

Taubenberger JK, Reid AH, Izon D, Boehme SA.

Department of Cellular Pathology, Armed Forces Institute of Pathology,
Washington, DC 20306, USA.

Transformed murine fetal thymocyte cell lines were derived by incubating fetal
thymic organ cultures with a v-myc/v-raf-containing retroviral construct in
order to model developmental stages within the early triple negative
(CD3-CD4-CD8-) thymocyte population. The resulting 10 cell lines had a lymphoid
morphology, were all CD44+, CD90+, and were triple negative by surface antigen
analysis. The cell lines, however, were distinguishable by differences in the
expression of T cell-associated and T cell-specific genes. The CD3 genes were
observed to be discoordinately expressed, in that CD3 gamma chain gene
expression was detected in 2 cell lines in the absence of CD3 delta and epsilon
expression. Expression of the CD3 gamma chain gene was observed in cell lines
without the expression of other T cell-specific genes or T cell receptor
rearrangement and may be one of the earliest T cell-specific genes to be
expressed. The transcription factor Ikaros was expressed in all 10 cell lines,
whereas the transcription factor TCF1 alpha was expressed only in the 2 most
differentiated lines. In 8 cell lines, expression of partial TCR beta and/or TCR
alpha transcripts was observed by Northern blot. In several lines, expression of
rearranged TCR alpha transcripts in the absence of TCR beta transcripts was
demonstrated; however, TCR beta DJ rearrangements were observed by Southern blot
in all but 1 of these cell lines. Thus, these cell lines, ordered based on the
general pattern of additive gene expression observed, may reflect various stages
of triple-negative thymocyte differentiation and provide an in vitro mechanism
to elucidate some of the molecular events involved in early thymocyte
development.

PMID: 8754860 [PubMed - indexed for MEDLINE]


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