Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using three antibodies (JG8, CM-1 and 1081) directed to the p53 protein, strong positivity was found in 16/47 (34.0%) of mucosal squamous cell carcinomas of the head and neck and in two squamous carcinoma cell lines (LICR-LON- HN5 and HN6Rr). The presence of the mutant p53 was confirmed in the cell lines as substitutions in exon 7 (codon 238, TGT greater than AGT) and exon 5 (codon 152, CCG greater than CTG) respectively. Positive staining was seen only in the undifferentiated cells and progressively lost as the cells keratinized, both in the tumour specimens and in the cell lines. Similar results were seen in areas of dysplasia, well removed from the site of the primary tumour. Staining of epidermal lesions showed positivity in 2/12 (16.6%) cases of Bowen's disease, 0/12 (0.0%) cases of solar keratosis, 0/10 (0.0%) basal cell carcinomas and in 3/20 (15.0%) squamous cell carcinomas. These results are discussed in relation to the multifocal origin of squamous cell carcinomas, the role of p53 mutations in squamous cell carcinomas from different sites and the significance of the 'basal' distribution of p53 as a normal growth regulator. The possible significance of the distribution of p53 in squamous epithelium as it relates to papilloma virus infection is also considered.
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PMID:Expression of p53 in premalignant and malignant squamous epithelium. 171 23

Abnormal degradation of beta-catenin caused by alteration of the glycogen synthase kinase-3beta (GSK-3beta) consensus motif is an important step for carcinogenesis. We hypothesize that beta- and gamma-catenin may play an important role in the pathogenesis of bladder cancer. We tested this hypothesis through analysis of beta- and gamma-catenin in both murine and human bladder cancers. A murine bladder cancer model was prepared by use of N-butyl-N-(-4-hydroxybutyl)nitrosamine (BBN) in 6-week-old male B6D2F1 mice. After 4, 8, 12, 16, 20, 24, and 28 weeks of BBN treatment, bladder specimens were harvested and analyzed for both protein and gene expression for beta- and gamma-catenin. Mutational analysis of the NH(2)-terminal regulatory domains of beta- and gamma-catenin was performed in each specimen by PCR-single-strand conformational polymorphism (SSCP) analysis. Mutations were further confirmed by direct DNA sequencing with a dye terminator method. Human bladder cancer specimens with normal tissues, dysplasia, carcinoma in situ, and carcinoma of grades, 1, 2, and 3 were also analyzed for beta- and gamma-catenin expression. beta- and gamma-catenin were analyzed for mutations by SSCP and direct DNA sequencing. Intracellular accumulation of beta- and gamma-catenin was observed in 6 of 20 invasive carcinoma specimens. There was no intracellular accumulation of beta- and gamma-catenin in mucosal dysplasia, papillary or nodular dysplasia, and carcinoma in situ specimens. On an SSCP analysis for beta-catenin, abnormal bandshifts were detected in two invasive carcinomas with intracellular beta-catenin accumulation. Further sequencing revealed two mutations [AGT(S) to ATT(I) and TCT(S) to CCT(P)] within the consensus motif for GSK-3beta phosphorylation. On the other hand, SSCP analysis for gamma-catenin followed by sequencing revealed three mutations in two invasive carcinomas with intracellular accumulation of gamma-catenin. These three alterations affected the 3' downstream region outside the GSK-3beta phosphorylation site [ACC(T) to GCC(A), CTC(L) to ATC(I), and CTC(L) to ATG(M)]. In human bladder cancer, beta- and gamma-catenin expression was significantly weaker than in normal bladder. On SSCP analysis one abnormal bandshift was observed in high-grade human bladder cancer with intracellular beta-catenin accumulation. DNA sequencing revealed mutation TCT(S) to TGT(C). In summary, alterations in beta- and gamma-catenin are late events favoring tumor progression in mouse BBN-induced bladder cancer. Changes affecting the GSK-3beta phosphorylation site appear to be associated with activation of beta-catenin, but not with activation of gamma-catenin. In human blabber cancer, beta- and gamma-catenin expression is similar to the expression in the mouse model. The present study demonstrates that beta- and gamma-catenin may play an important role in bladder cancer progression.
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PMID:Alterations of beta- and gamma-catenin in N-butyl-N-(-4-hydroxybutyl)nitrosamine-induced murine bladder cancer. 1158 41

Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.
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PMID:Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation. 1207 25

We report on a 15-year-old girl who presented with pituitary hypoplasia, os odontoideum, renal dysplasia, an asymmetrically short right leg, and postaxial hypodactyly of the right foot. Her endocrinological data showed anterior pituitary hormone deficiency. The fact that she had healthy parents and an elder sister suggests that she had either a de novo mutation or autosomal recessive inheritance. We speculated that bone morphogenetic protein 4 (BMP4), BMP2, or pituitary homeobox 1 (PTX1) might be the responsible genes in this patient based on the similarity of her clinical symptoms and phenotypes to knock-out mice of these genes. We performed mutation analysis of these genes by direct sequencing of genomic DNA. In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected. In PTX1 gene, transversion of GCC right curved arrow GGC in exon 2, converting alanine to glycine at codon 184 was found in the patient and controls. We did not find any non-sense mutations although 5 polymorphisms of these genes were found. This constellation of findings may represent a new entity of congenital combined pituitary hormone deficiency.
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PMID:Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia, os odontoideum, renal dysplasia, and right leg anomalies. 1216 3

The aim of this study was to clarify the histogenesis of Barrett's cancer. First, 28 lesions of the super-minute dysplasia <or= 1 mm in diameter were detected by pathological examinations for Barrett's esophagus. Secondly, the K-ras codon 12 mutations in these super-minute neoplasias of the Barrett's esophagus were examined by DNA extraction using a microdissection. It was found that seven of 28 (25%) super-minute dysplasia lesions in the Barrett's esophagus showed K-ras mutation, and were a single mutation, with AGT being detected in three lesions and GAT being detected in four lesions. Also, these dysplasia lesions could be divided into two groups according to p53-LI. Two among three lesions with p53-LI over 90%, which were considered to be morphologically high grade dysplasia or intramucosal adenocarcinoma, showed K-ras mutations (both lesions: GGT-->AGT), and 5 among 25 lesions with an average p53-LI of 58%, which were considered to be morphologically low grade dysplasia, showed K-ras mutation (four lesions: GGT-->GAT, 1 lesion: GGT-->AGT). This current study shows that some dysplasia lesions have K-ras mutations in their initial condition, whether these atypical tubule lesions are low grade dysplasia or high grade dysplasia (intramucosal adenocarcinoma), and supports the dysplasia-carcinoma sequence in the histogenesis of Barrett's cancer and synchronously suggests that there is a different route to it.
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PMID:K-ras codon 12 mutations of the super-minute dysplasia in Barrett's esophagus by DNA extraction using a microdissection method. 1464 12