1: Genomics. 2004 Feb;83(2):231-42. 

Cloning of the rat beta-catenin gene (Ctnnb1) promoter and its functional
analysis compared with the Catnb and CTNNB1 promoters.

Li Q, Dashwood WM, Zhong X, Al-Fageeh M, Dashwood RH.

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.

Considerable recent interest has focused on the stabilization and accumulation
of beta-catenin protein in human and animal tumors and the corresponding
activation of downstream beta-catenin/TCF/LEF target genes. However, there is
only sparse information on the regulation of beta-catenin expression at the
transcriptional level and its possible involvement in physiological and
pathophysiological processes. We report here the cloning and characterization of
a 3.6-kb promoter fragment from the rat beta-catenin gene, Ctnnb1, and its
comparison with corresponding promoters from the mouse and human genes, Catnb
and CTNNB1. Several AP1 binding sites were confirmed in the promoters of all
three species using mobility shift and reporter assays, and one putative TCF/LEF
site also was observed in the promoter of CTNNB1. Subsequently, protein/DNA
array analyses identified numerous other transcription factors through their
high-affinity binding to the Ctnnb1 promoter, including E2F1, NFkappaB, MEF1,
Pax5, ISRE2, Smad3/4, GATA, and ZIC. The strong binding of E2F1 and NFkappaB is
especially noteworthy, because the former transcription factor is regulated by
cyclin D1, a downstream target of beta-catenin/TCF/LEF signaling, whereas the
latter transcription factor has been implicated in "cross talk" between the Wnt
and the NFkappaB signaling pathways. These results are discussed in terms of
their implications for human cancer development and specifically the various
tumors in which beta-catenin mRNA is overexpressed, as well as for embryonic
development, when reversible changes in beta-catenin expression occur in
response to secreted Wnt ligands. The findings reported here should provide
important avenues for further research focused on the regulation of Ctnnb1
activity, including the ability of beta-catenin/Tcf downstream targets to
modulate beta-catenin expression at the transcriptional level.

PMID: 14706452 [PubMed - indexed for MEDLINE]


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2: Clin Cancer Res. 1995 Feb;1(2):207-14. 

PAX5 expression correlates with increasing malignancy in human astrocytomas.

Stuart ET, Kioussi C, Aguzzi A, Gruss P.

Department of Molecular Cell Biology, Max-Planck Institute for Biophysical
Chemistry, Am Fassberg, 37077 Gottingen, Germany.

Rearrangements concerning chromosome 9p are a late event in the progression of
human astrocytic tumors to their most malignant form. The expression of PAX5,
which maps to chromosome 9p13, was studied in primary human brain tumors of
astrocytic origin. Whereas murine Pax5 is not expressed in the forebrain at any
stage, PAX5 expression was increased in a range of astrocytomas (WHO grades
II-IV) which originated in the forebrain. Expression of PAX5 was limited to
those cells which also expressed the oncogenes myc, fos, or jun singularly or in
combination. The epidermal growth factor receptor was highly expressed in
glioblastoma multiform tumors in areas which were also highly PAX5 positive. We
conclude that the missappropriate expression of PAX5 may aid in promoting the
progression of astrocytomal malignancy.

PMID: 9815975 [PubMed - indexed for MEDLINE]


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