p53 regulates the expression of the tumor suppressor gene maspin.
Maspin has been shown to inhibit tumor cell invasion and metastasis in breast tumor cells. Maspin expression was detected in normal breast and prostate epithelial cells, whereas tumor cells exhibited reduced or no expression. However, the regulatory mechanism of maspin expression remains unknown. We report here a rapid and robust induction of maspin expression in prostate cancer cells (LNCaP, DU145, and PC3) and breast tumor cells (MCF7) following wild type p53 expression from an adenovirus p53 expression vector (AdWTp53). p53 activates the maspin promoter by binding directly to the p53 consensus-binding site present in the maspin promoter. DNA-damaging agents and cytotoxic drugs induced endogenous maspin expression in cells containing the wild type p53. Maspin expression was refractory to the DNA-damaging agents in cells containing mutant p53. These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), define a new category of molecular targets of p53 that have the potential to negatively regulate tumor invasion and/or metastasis.
Duke Scholars
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- Ultraviolet Rays
- Tumor Suppressor Protein p53
- Tumor Cells, Cultured
- Serpins
- RNA, Messenger
- Proteins
- Prostatic Neoplasms
- Promoter Regions, Genetic
- Neoplasm Metastasis
- Male
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ultraviolet Rays
- Tumor Suppressor Protein p53
- Tumor Cells, Cultured
- Serpins
- RNA, Messenger
- Proteins
- Prostatic Neoplasms
- Promoter Regions, Genetic
- Neoplasm Metastasis
- Male