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

The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple tumour types including colorectal carcinomas. Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated). In addition, we examined whether the Fragile histidine triad and mismatch repair protein expression correlated with p53 expression and clinicopathological findings. Significant loss or reduction of Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately-differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being significantly higher in the latter than that in the former two (P<0.0001). Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile histidine triad and mismatch repair protein expression was not significantly associated with p53 expression. These results suggested that reduced Fragile histidine triad expression might be correlated with mismatch repair expression, but not with p53 expression.
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PMID:Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma. 1217 81

There is limited information on the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). The Fragile Histidine Triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in a variety of human malignancies. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins. We analyzed Fhit and Mlh1 protein expressions using immunohistochemical methods in 20 GBCs and three gallbladder adenomas (GBAs) to elucidate the role of Fhit protein in gallbladder carcinogenesis. In addition, we examined whether Fhit and Mlh1 protein expressions correlated with P53 expression and clinicopathological findings. Significant loss or reduction in Fhit expression was noted in nine (45%) of the GBCs and one of the GBAs. Loss of Mlh1 protein expression was detected in six (30%) of the GBCs and one of the GBAs. Reduced Fhit expression was significantly associated with the absence of Mlh1 protein expression in the GBCs and the GBAs (p=0.0186). P53 overexpression was present in 11 (55%) of the GBCs, but none of the GBAs. Fhit and Mlh1 protein expressions were not significantly associated with P53 expression and clinicopathological findings. These results suggested that reduced Fhit expression might be involved in the development of GBC and be correlated with Mlh1 expression.
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PMID:Expression of Fhit, Mlh1, and P53 protein in human gallbladder carcinoma. 1296 85

Triad 1 (2 RING [really interesting new gene] fingers and DRIL [double RING finger linked] 1) is an E3 ligase that induces apoptosis and clonogenic inhibition in myeloid cells through Gfi-1 stabilization. Here we demonstrate that Triad 1 induces apoptosis in several cancer cell lines including MCF7, A549, U2OS, and HCT 116 p53(+/+) cells via its RING ligase activity. Interestingly, in these cancer cells, Triad 1-induced apoptosis is not mediated by Gfi-1 stabilization but is instead p53-dependent. Moreover, Triad 1 promotes transactivation of p53. These results suggest that Triad 1 can induce apoptosis through its ligase activity via p53 activation.
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PMID:Triad 1 induces apoptosis by p53 activation. 2022 83

The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma (CRC). However, the mechanism triggered by the serrated pathway remains unclear. Therefore, to clarify the molecular and clinicopathological characteristics of the serrated tumorigenic pathway, immunohistochemistry was used to examine the expression of Fragile Histidine Triad (FHIT), cyclooxygenase-2 (COX-2), MutL homolog 1 (MLH1), MutS protein homolog 2 (MSH2) and P53 in endoscopically resected samples of 62 serrated polyps. These samples included 20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs), 26 sessile serrated adenoma/polyps (SSA/Ps), 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure CRCs without any adenoma component (EPCs). FHIT expression was markedly reduced or absent in 50% of TSA samples, 92.3% of SSA/Ps and 44% of EPCs, but only rarely in HPs, non-serrated adenomas and CIAs. COX-2 expression was more common in non-serrated adenomas compared with in serrated polyps, and was present in 25 and 3.2% of the cases respectively (P<0.01). Furthermore, COX-2 expression was more frequent in CIAs (60%) compared with in EPCs (22.2%; P<0.05). The incidence of negative COX-2 expression was higher in FHIT-negative SSA/Ps compared with in FHIT-positive SSA/Ps (P=0.08). A total of 16.7% of EPC samples and 11.5% of SSA/Ps demonstrated a loss of MLH1/MSH2 expression, but none of the other tumor types did. P53 overexpression was significantly increased in EPC (77.8%) and CIA (60%) samples compared with in HP (0%), TSA (6.6%), SSA/P (0%) and non-serrated adenoma (10%) samples (P<0.01). These findings demonstrated that there are different expression patterns between the serrated pathway and ACS, indicating that aberrant FHIT and inhibited COX-2 expression may be associated with serrated tumorigenesis. In addition, this data indicated that EPC may contain tumors derived from the serrated pathway as well as ACS.
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PMID:Protein expression of Fragile Histidine Triad and cyclooxgenase-2 in serrated neoplasia of the colorectum. 2892 31