Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since human trophoblast undergoes extensive proliferation and exhibits invasive growth comparable to that of a malignant tumour, human placenta at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased expression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of the epidermal growth factor receptor have been described in the literature. Staining was also occasionally seen in trophoblast invading the myometrium. It is most likely that immunohistochemically detectable expression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene, which could be a mechanism for controlling trophoblast proliferation.
Placenta 1995 Jan
PMID:Expression of the p53 tumour suppressor gene in human placenta: an immunohistochemical study. 771 22

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively). In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation.
Placenta 2000 Jan
PMID:Expression of the p53 gene and apoptosis in gestational trophoblastic disease. 1069 52

Gestational trophoblastic disease (GTD) is a heterogeneous group of diseases characterized by abnormally proliferating trophoblastic tissues. This includes partial and complete hydatidiform moles, invasive mole, choriocarcinoma and placental site trophoblastic tumour. Cytogenetic studies revealed that hydatidiform moles contain either solely (as in complete moles) or an excess (as in partial moles) of paternal contribution to the genome. Genomic imprinting is believed to play a pivotal role in the pathogenesis of hydatidiform moles. However its precise role and mechanism remains poorly understood. Hydatidiform mole carries a potential of malignant transformation. Similar to other human cancers, malignant transformation in gestational trophoblastic tumours is likely a multistep process and involves multiple genetic alterations including activation of oncogenes and inactivation of tumour suppressor genes. In addition, expression of telomerase activity, altered expression of cell--cell adhesion molecules and abnormal expression of matrix metalloproteinases have also been reported in GTD. These represent disruption of the delicate balance and regulation of cellular processes including proliferation, differentiation, apoptosis and invasion. The significance of these alterations in the pathogenesis and malignant transformation of gestational trophoblastic diseases is reviewed in this paper.
Placenta 2002 Jan
PMID:Current understandings of the molecular genetics of gestational trophoblastic diseases. 1186 89

Identification of factors that play a role in regulating the highly invasive ability of human placental cells throughout gestation will contribute to a better understanding of this unique developmental process. The aims of this study were to determine whether the tumour suppressor gene maspin is present in the human placenta and plays a putative role in the regulation of cytotrophoblast invasion during placental development. The data showed that the expression of maspin mRNA was maximum in term placentae compared to the first and second trimester tissues, and absent in the HTR-SVneo (immortalized extravillous cytotrophoblast), JEG-3 and JAR (choriocarcinoma) cell lines. Maspin protein, detected by Western blot analysis, was twofold higher in the second trimester and 4.4-fold higher in the third trimester compared to the first trimester. Maspin immunohistochemical staining was localized in cytotrophoblasts with increased and more diffuse staining in the second and third trimesters. Corresponding to the period of maximum maspin expression, cytotrophoblasts isolated from term placentae had significantly lower invasive ability as compared to first and second trimester cytotrophoblasts (P< 0.03). Further, addition of recombinant maspin significantly decreased cytotrophoblast invasion in vitro by 40-50 per cent in all three trimesters of gestation. This study provides the first evidence of the temporal expression of maspin during human gestation and suggests a putative role for maspin in regulating the invasive activity of cytotrophoblasts at term. The down-regulation of maspin expression may be critical at the time of implantation and early placental development, whereas upregulation of maspin may serve as a signal for the end of cytotrophoblast invasion and gestation.
Placenta 2002 Apr
PMID:The tumour suppressor gene maspin is differentially regulated in cytotrophoblasts during human placental development. 1196 37