Abstract
The p27(Kip1) is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27(Kip1) and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27(Kip1). This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27(Kip1) promoter. These results suggest that the transcriptional regulation of p27(Kip1) by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.
MeSH terms
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Adenocarcinoma / pathology
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Animals
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BRCA1 Protein / chemistry
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BRCA1 Protein / physiology*
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Breast Neoplasms / pathology
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COS Cells / metabolism
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Carcinoma, Ductal, Breast / pathology
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Cell Cycle
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Cell Cycle Proteins / biosynthesis
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Cell Cycle Proteins / genetics*
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Chlorocebus aethiops
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Colonic Neoplasms / pathology
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Cyclin-Dependent Kinase Inhibitor p27
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Female
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Gene Expression Regulation, Neoplastic
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Genes, BRCA1
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Genes, Reporter
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Humans
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Mice
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Neoplasm Proteins / metabolism
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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Sequence Deletion
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Transcriptional Activation*
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Transfection
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Tumor Cells, Cultured / metabolism
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Tumor Suppressor Proteins / biosynthesis
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Tumor Suppressor Proteins / genetics*
Substances
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BRCA1 Protein
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Neoplasm Proteins
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27