Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:p53 regulates the expression of the tumor suppressor gene maspin. 1069 90

Maspin (mammary serpin) is a novel serine protease inhibitor related to the serpin family with a tumor-suppressing function in breast cancer. Maspin was originally identified from normal mammary epithelium by subtractive hybridization and might function as a class II tumor-suppressor gene. Maspin's decreased expression with increased level of malignancy and its loss in metastatic cells is regulated at the transcriptional level. Cytosin methylation and heterochromatinization in the promoter region might account for this down-regulation of maspin. Transfection of tumor cells with maspin cDNA inhibits invasion and motility and decreases tumor growth and metastatic ability in nude mice. Maspin interacts with the p53 tumor-suppressor pathway and function as an inhibitor of angiogenesis in vitro and in vivo. The progressive loss of expression of maspin during tumor progression makes this new protein an interesting diagnostic and prognostic marker. The re-expression of maspin by pharmacological intervention potentially offers a promising approach as a therapeutic option in breast cancer therapy.
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PMID:Maspin--a novel protease inhibitor with tumor-suppressing activity in breast cancer. 1120 99

The serine protease inhibitor Maspin has been reported to inhibit the invasiveness and motility of prostate cancer tumor cells. Additionally, a p53-dependent regulatory pathway of Maspin in prostate cancer cell lines has been indicated. The first aim of our study was to determine the prognostic value of Maspin protein expression for the recurrence-free survival of patients undergoing radical prostatectomy for the treatment of clinically localized prostate cancer. Secondly, Maspin expression was correlated to p53 protein expression in order to gain additional information on a possible and previously suggested regulatory influence of the wild-type p53 protein on the Maspin protein expression. Tumor specimens obtained from 84 patients undergoing radical prostatectomy for localized prostate cancer were investigated for the expression of the Maspin and p53 protein by an immunohistochemic approach. Maspin protein expression was correlated with further patients' and tumor characteristics such as tumor stage, histologic grading, regional lymph node status, p53 protein expression and recurrence-free survival of the patients following radical prostatectomy. After a median follow-up of 64 months (24-197 months), 23 of 40 patients (58%) with a negative or decreased Maspin expression (group 1) developed local recurrence or systemic tumor progression in contrast to 8 of 44 patients (18%) with a retained expression of the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurrence-free survival following radical prostatectomy was 26 months (12-37 months) for group 1 patients and 41 months (5-134 months) for patients from group 2 (p = 0.04). A positive immunohistochemic staining reaction for the p53 protein was significantly correlated with a decreased expression of the Maspin protein (p = 0.015; Spearman correlation coefficient). Additionally, loss of Maspin protein expression was correlated to higher tumor stages (p = 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is the first study to indicate that Maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing the local invasiveness and further systemic progression of prostate cancer. Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer.
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PMID:Expression of the p53 and Maspin protein in primary prostate cancer: correlation with clinical features. 1149 36

Maspin is a member of serpin family with tumor suppressing activity. Initially identified from normal mammary epithelial cells, maspin expression was down-regulated in breast tumor cells by both in vitro assay and by immunostaining of clinical specimen from breast cancer patients. Recently, maspin research has been advanced to clinical research aimed at correlating the tumor progression with the expression level of maspin in breast cancers. However, due to the variation and large sample sizes, no comparison study of maspin expression has been done using various normal and tumor samples. The tissue microarray is a technique recently developed for the standardization and high-throughput screening of clinical markers. We have used the tissue microarray to examine the maspin expression in various normal tissues and cancers. Our data indicated that maspin was expressed at different level in most of human tissues in the array. However, maspin expression was consistently down-regulated during tumor progression. There were no obvious correlation between maspin expression and tumor grades, nor was there any correlation with the age of patients. Since wild-type p53 was found to activate maspin promoter in vitro, we examined weather there was a connection between p53 level and maspin expression in vivo. Our data indicate that maspin expression inversely correlates with mutant p53 level in majority of cancer, suggesting maspin is likely a p53 target gene in vivo.
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PMID:Tissue microarray analysis of maspin expression and its reverse correlation with mutant p53 in various tumors. 1201 91

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 +/- 54.2) than those of the negative maspin expression groups (256.1 +/- 75.4,P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvessel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.
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PMID:Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density. 1218 37

Maspin (mammary serpin) is an inhibitor of serine proteases with tumor suppressor activity in breast cancer. Maspin was originally identified by subtractive hybridization in normal breast epithelial cells, but its expression decreased during tumor progression. The loss of maspin gene expression with increasing malignancy is by transcriptional regulation. Maspin is known to be involved in invasion and metastasis, interact with the p53 tumor suppressor pathway, and act as an inhibitor of angiogenesis. The immunohistochemical analysis and reverse-transcription polymerase chain reaction of maspin in normal human breast tissue and breast carcinoma indicated a stepwise reduction of maspin expression during the progression from ductal carcinoma in situ to invasive carcinoma to lymph node metastasis. The lack of maspin expression in breast cancer seems to be associated with a short disease-free survival and supports maspin's function as an indicator for tumor aggressiveness and metastatic potential. New studies on the gene regulation of maspin provide evidence for promising potential of possible re-expression of maspin in tumor cells. The function of maspin as a tumor suppressor gene involved in tumor invasion, metastasis, and angiogenesis may not be limited to breast cancer.
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PMID:Expression and regulation of tumor suppressor gene maspin in breast cancer. 1253 66

p53 is an important transcriptional regulator that is frequently mutated in cancer. Gene-profiling experiments of breast cancer cells infected with wt p53 revealed both MASPIN and desmocollin 3 (DSC3) to be p53-target genes, even though both genes are silenced in association with aberrant cytosine methylation of their promoters. Despite the transcriptional repression of these genes by aberrant DNA methylation, restoration of p53 resulted in the partial reactivation of both genes. This reactivation is a result of wt p53 binding to its consensus DNA-binding sites within the MASPIN and DSC3 promoters, stimulating histone acetylation, and enhancing chromatin accessibility of their promoters. Interestingly, wt p53 alone did not affect the methylation status of either promoter, suggesting that p53 itself can partially overcome the repressive barrier of DNA methylation. Pharmacologic inhibition of DNA methylation with 5-aza-2'-deoxycytidine in combination with restoration of wt p53 status resulted in a synergistic reactivation of these genes to near-normal levels. These results suggest that cancer treatments that target both genetic and epigenetic facets of gene regulation may be a useful strategy towards the therapeutic transcriptional reprogramming of cancer cells.
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PMID:Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression. 1278 71

The serine protease inhibitor maspin has been reported to inhibit invasiveness and motility of tumor cells. Additionally, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. In a pre-study we were able to detect maspin protein in papillary thyroid carcinomas (PTC), whereas normal (tumor-free) thyroid tissue, follicular adenomas, follicular carcinomas, poorly differentiated carcinomas and undifferentiated carcinomas of the thyroid were maspin-negative. The first aim of our study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of PTC patients undergoing radical thyroidectomy and postoperative irradiation. Secondly, maspin expression was correlated to p53 protein expression in order to gain additional information on a possible regulatory influence of the wild-type p53 protein on maspin. An immunohistochemical approach study was performed on 68 tumor specimens. Maspin protein expression was detectable in 48 of 68 patients (71%; M+). After a median follow-up of 81 (26-117) months the median recurrence-free survival was 60 (28-117) months for M+ and 42 (11-108) months for M- (p=0.03). After 110 months 83% of patients had recurrence-free disease in M+, whereas in M- only 40% of patients were recurrence-free. The median long-term survival was 81 (42-108) months for M+ and 55 (21-99) months for M- (p=0.03). After 5 years, M+ and M- patients had a total survival of 98 and 80%, and after 9 years 90 and 60%, respectively. Mutant-type p53 expression was detectable in 17 of 68 PTC (25%). Mt p53 was positive in 1 of 47 M+ (2%) compared with 16 of 20 M- (80%, p<0.01). This study indicates that maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing local invasiveness and further systemic progression of papillary thyroid carcinomas. Our data hint of a p53-dependent regulatory pathway of the maspin protein in human cancer.
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PMID:Maspin in thyroid cancer: its relationship with p53 and clinical outcome. 1453 96

Maspin inhibits metastasis of some cancer cells, and clinical studies have identified correlations between maspin loss and poor prognosis in several cancer types. Maspin was found to be significantly overexpressed in lung cancer samples as compared with matched normal lung tissues. However, the regulatory mechanism of maspin expression remains unclear. We show here that differential expression of maspin in carcinoma-derived lung cancer cells is regulated at the transcriptional level. We found that p63 is a critical factor for the transcription of maspin, which is lost in highly invasive cancer cells such as NCI-H157, NCI-322, and NCI-358. No correlation was found between maspin expression and the previously associated transcription factors, p53, Ets1, and Pdef. Instead, maspin expression was strictly dependent on the presence of p63 in lung cancer tissues (P < 0.001) and in the tested cell lines. Transient expression of p63 transactivated the maspin promoter with remarkable fold changes in cells expressing the TAp63, suggesting that TAp63 might be a novel stimulator of the maspin promoter in lung cancer. We have also demonstrated the binding of p63 protein to a previously identified p53-binding site on the maspin promoter by gel shift and chromatin immunoprecipitation assays. In tumor tissues, maspin expression was associated with lymph node involvement (P = 0.035) and tumor stage (P = 0.063) in all tested cases, except squamous carcinoma. In terms of function, ectopic expression of maspin inhibited cell invasion in squamous carcinoma as well as adenocarcinoma. Taken together, these results define maspin as a new molecular target of p63 that eventually inhibits the invasion of lung cancer.
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PMID:Maspin expression is transactivated by p63 and is critical for the modulation of lung cancer progression. 1546 79

Maspin, a serine protease inhibitor related to the serpin family, was originally identified in normal mammary epithelium. Reduced expression of maspin is related with development, invasion and metastasis of certain human cancers. In the present study, the expression of maspin was examined in gastric mucosa, adenoma and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa, maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic glandular cells and pyloric glandular cells. Maspin expression was lost in 71% (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss of maspin expression was significantly associated with poorly differentiated histology, advanced stage and deep invasion (P<0.001). There was an inverse correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA expression was lost in all of 8 gastric carcinoma cell lines that was retrieved after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell lines. These results suggest that loss of maspin expression partly due to DNA methylation may participate in tumor development and progression of gastric carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a biological marker of high-grade malignancy.
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PMID:Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality. 1549 82


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