In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 1 ( 2001-01-02), p. 130-135
Abstract:
Expression of the breast and ovarian cancer susceptibility gene BRCA1 is down-regulated in sporadic breast and ovarian
cancer cases. Therefore, the identification of genes involved in the regulation of BRCA1 expression might lead to new
insights into the pathogenesis and treatment of these tumors. In the present study, an “inverse genomics” approach based on a
randomized ribozyme gene library was applied to identify cellular genes regulating BRCA1 expression. A ribozyme gene library
with randomized target recognition sequences was introduced into human ovarian cancer-derived cells stably expressing a selectable marker
[enhanced green fluorescence protein (EGFP)] under the control of the BRCA1 promoter. Cells in which BRCA1 expression was upregulated by particular ribozymes were selected
through their concomitant increase in EGFP expression. The cellular target gene of one ribozyme was identified to be the dominant negative
transcriptional regulator Id4 . Modulation of Id4 expression resulted in inversely regulated
expression of BRCA1 . In addition, increase in Id4 expression was associated with the ability of cells
to exhibit anchorage-independent growth, demonstrating the biological relevance of this gene. Our data suggest that Id4 is a
crucial gene regulating BRCA1 expression and might
therefore be important for the BRCA1 regulatory pathway
involved in the pathogenesis of sporadic breast and ovarian cancer.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.98.1.130
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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