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.
Zou
Z
Z
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. zzou@usuhs.mil
Gao
C
C
Nagaich
A K
AK
Connell
T
T
Saito
S
S
Moul
J W
JW
Seth
P
P
Appella
E
E
Srivastava
S
S
D000256:Adenoviridae / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015843:Serpins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide