Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure in utero to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of reproductive-tract malignancies in female offspring. To search for the genetic targets of DES, representational difference analysis was used to compare genomic DNA from DES-associated mouse uterine adenocarcinoma cells with genomic DNA from normal CD-1 mouse tissue. Several difference clones were obtained, all of which recognized rearranged and amplified sequences in tumor compared with normal DNA. One of these difference fragments mapped to a region of mouse chromosome 10 that includes the mdm2 oncogene. Amplification and overexpression of mdm2 was found in all three early-passage cell lines established from independent DES-associated cancers. These findings demonstrate the potential power of representational difference analysis in cancer research and suggest a genetic mechanism for DES-induced carcinogenesis.
Mol Carcinog 1994 Sep
PMID:Use of representational difference analysis for the identification of mdm2 oncogene amplification in diethylstilbestrol-induced murine uterine adenocarcinomas. 791 85

Matrilysin, which is a member of the matrix metalloproteinase family and is implicated in colon cancer invasion, is expressed in human colon adenocarcinoma-derived SW1116 cells. We investigated the effect of alpha-difluoromethylornithine (DFMO) on matrilysin expression in this cell line because others have shown that DFMO can inhibit invasion and carcinogenesis in epithelial tissues, including the colon, in experimental models. DFMO reduced extracellular levels of matrilysin protein after 4 d of treatment. Intracellular levels of matrilysin protein were minimally affected by DFMO treatment. The decrease in extracellular matrilysin protein levels caused by DFMO was not a consequence of lowered steady-state levels of matrilysin mRNA. After 4 d of exposure, the amount of this transcript was higher in DFMO-treated cells than in untreated cultures, whereas the mRNA stabilities were similar. These data show that polyamine depletion by DFMO can suppress the expression of matrilysin, a gene product thought to be involved in tumor invasion. The decrease in extracellular matrilysin protein caused by DFMO treatment appears to be due to a posttranscriptional mechanism, although transcription of this gene also seems to be affected by polyamines in SW1116 cells.
Mol Carcinog 1994 Nov
PMID:Polyamine-dependent expression of the matrix metalloproteinase matrilysin in a human colon cancer-derived cell line. 794 2

Several functions of alveolar macrophages (AM) are modified by cigarette smoking. AM are the first line of defense in bronchoalveolar spaces and could be depressed in their cytotoxicity to tumor cells in smokers. An assay using A549 cells (human lung adenocarcinoma) as target cells was performed to assess cytostasis mediated by AM and their supernatants (SN) from healthy smokers (n = 8) and nonsmokers (n = 6). Contact-mediated cytostasis was decreased in AM of smokers (n = 8) relative to nonsmokers (n = 6) (22.9 +/- 5.7% versus 42.7 +/- 6.0% [+/- SEM], P < 0.04) and increased after lipopolysaccharide (LPS) stimulation in both groups (34.5 +/- 5.3% versus 46.8 +/- 5.2%, NS). Cytostasis induced by SN from nonstimulated AM was low in both groups and was still lower in smokers after LPS exposure (19.3 +/- 4.5% versus 34.5 +/- 4.8%, P < 0.04). Among cytotoxic factors produced by macrophages, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) may play an important role in cytostasis. Recombinant human (rH) IL-1 beta and rHTNF alpha had a moderate cytostatic activity, which was additive, whereas rHIL-6 had no significant activity on A549 cells. Bioactive IL-1 beta, IL-6, and TNF alpha were therefore measured in macrophage SN. Their levels tended to be lower in smokers than in nonsmokers and were much increased after LPS stimulation. Levels of the three cytokines were also found to correlate with each other; furthermore, a good correlation between cytokine levels in SN and cytostasis was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Nov
PMID:Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha. 794 92

Mucin glycoproteins (mucins) are the major macromolecular constituents of mucus gels in mammalian respiratory, gastrointestinal, and reproductive tracts. Disorders of mucin glycosylation, which may result from either abnormal post-translational processing or differences in mucin protein gene expression, have been indicated in several diseases. Quantitation of mucin gene expression has been hindered by two features of human mucin genes: variable numbers of tandemly repeating nucleotides per mRNA molecule and polydisperse mRNA transcripts. We report here a method to quantitate mucin mRNA levels in epithelial cells and have evaluated three mucin genes, MUC1, MUC2, and MUC5, which are expressed in respiratory epithelium. The method uses the 3' non-tandem repeat mucin cDNA sequences, as they were shown to have a single-size transcript when amplified by the polymerase chain reaction, consistent with a one-to-one relationship with the mRNA molecule. The 3' non-tandem repeat cDNA sequences were cloned and transcribed in vitro to prepare complementary RNA (cRNA) standards. By comparison to a cRNA standard curve, mucin gene expression was evaluated in colon adenocarcinoma, pancreatic adenocarcinoma, and transformed respiratory epithelial cells and in nasal polyp tissue by slot blot analysis. CFPAC-1, a pancreatic adenocarcinoma cell line, expressed the highest MUC1 transcript levels. Colon adenocarcinoma cell lines varied in MUC2 expression levels, and one colon adenocarcinoma cell line, HT-29, had higher levels of MUC5 than MUC2. Nasal polyp tissue expressed more MUC5 mRNA than MUC1 or MUC2 mRNA. This mucin mRNA slot blot method provides a quantitative method for investigating the regulation of mucin gene expression in health and disease.
Am J Respir Cell Mol Biol 1994 Dec
PMID:Quantitation of mucin mRNA in respiratory and intestinal epithelial cells. 794 2

The structures of cDNA clones encoding four members of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) family were characterized. The rat type I, type II and the novel type IV are genuine NAD+/H-dependent 3 beta-HSD isoenzymes. On the other hand, the liver-specific type III protein is a specific 3-keto-reductase (3-KSR) that catalyzes the conversion of 5 alpha-androstane-3-one-17 beta-ol (DHT) and 5 alpha-androstane 3,17-dione (A-dione) into their 3 beta-hydroxy metabolites. The aim of the present study was to further characterize the enzymatic properties of rat types I, III and IV, especially their role in the formation and degradation of DHT after transient expression in intact human HeLa cervical carcinoma, JEG-3 choriocarcinoma or SW-13 adrenal cortex adenocarcinoma cells in culture. The expressed type III 3-KSR in intact HeLa cells catalyzed the reduction of DHT into 3 beta-diol, whereas expression of type I 3 beta-HSD in these cell lines had no significant effect on the basal conversion of DHT into 3 beta-diol, but it did increase the formation of DHT from 3 beta-diol. A-dione is the predominant product obtained when DHT and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) are used as substrates in intact JEG-3 and SW-13 cells transfected with rat type I 3 beta-HSD. Furthermore, this predominant 17 beta-HSD activity was also observed in SW-13 cells transfected with the novel rat type IV 3 beta-HSD. The predominance of this 'secondary' 17 beta-HSD activity is also reflected in HeLa cells transfected with type I 3 beta-HSD by the deduced predominant pathway 3 beta-diol-->DHT-->5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol)-->androsterone (ADT), in which formation of 3 alpha-HSD activity of HeLa cells, whereas the other reactions are catalyzed by the type I 3 beta-HSD isoenzyme. This observation thus demonstrates that rat type I 3 beta-HSD may also catalyze the conversion of 3 alpha-diol into ADT through its intrinsic 17 beta-HSD activity. The predominant metabolic pathways observed in the present study could be attributed to preponderant bioavailability of NAD+ and NADPH in the intact transfected cells used.
Mol Cell Endocrinol 1994 Jul
PMID:Formation and degradation of dihydrotestosterone by recombinant members of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase family. 795 95

Protein tyrosyl phosphorylation plays an essential role in regulating cellular events such as proliferation, differentiation and oncogenesis. The recent characterization of the family of protein tyrosine phosphatases (PTPases) suggests that dephosphorylation might be a crucial event in these phenomena. One of the functions of PTPases is to reverse the effect of protein tyrosine kinases (PTKases), many of which are oncogenes, suggesting that they may act as tumor suppressors as described for HPTP gamma. In order to investigate the implication in lung cancer of HPTP beta, a receptor PTPase, we have developed a semi-quantitative method derived from primer-directed reverse transcription (RT) and subsequent polymerase chain reaction (PCR) with 32P-labelled nucleotide. We have demonstrated that the expression of HPTP beta mRNA was dramatically decreased in lung adenocarcinomas and lung malpighian carcinomas as compared to normal lung tissue. In addition, HPTP beta was not expressed in the pulmonar adenocarcinoma cell line A427, which proliferates in a deregulated way. These results suggest that the loss of expression of HPTP beta might play a role in neoplasic transformation and thus this molecule could act as a tumor suppressor factor.
Cell Mol Biol (Noisy-le-grand) 1994 Jul
PMID:Implication of a protein-tyrosine-phosphatase in human lung cancer. 798 22

Platelet-activating factor (PAF) is a phospholipid actively produced by human endometrium and deeply involved in the processes of ovoimplantation and labor. We recently found that PAF represents a new autocrine growth factor for a human adenocarcinoma cell line, HEC-1A. Indeed, biologically active PAF is synthesized by HEC-1A cells, under progesterone control. In HEC-1A cells, PAF regulates intracellular calcium concentration ([Ca2+]), DNA synthesis and expression of early oncogenes. All these effects are blocked by the receptor antagonist L659,989. However, while nanomolar concentrations of PAF mobilize [Ca2+], only micromolar concentrations affect cell growth, suggesting heterogeneity of PAF receptors or signaling. Two distinct populations of PAF receptors are present in HEC-1A cells, which bind PAF in nanomolar and micromolar concentrations, respectively. Since HEC-1A cells are producing elevated concentrations of PAF and micromolar concentrations of the PAF antagonist L659,989 inhibit cell proliferation, an autocrine role for PAF is suggested in HEC-1A cells.
J Steroid Biochem Mol Biol 1994 Jun
PMID:Platelet-activating factor in human endometrium. 804 1

The human gastric bacterial pathogen Helicobacter pylori has been implicated in type B gastritis, peptic ulceration and gastric adenocarcinoma. Here we report on the cloning and genetic characterization of an H. pylori gene named vacA, which encodes the vacuolating cytotoxin VacA, a novel type of antigenic bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells. The vacuolating cytotoxin activity is expressed by a subset of clinical isolates (Vac+), all of which produce the 87 kDa cytotoxin antigen, but strains which produce neither the activity nor the cytotoxin protein (Vac-) also carry the gene. Isogenic H. pylori mutants in vacA generated by transposon shuttle mutagenesis produce neither the VacA antigen nor a vacuolating activity in a cell culture model. The vacA gene itself encodes a precursor protein of 139.6 kDa consisting of a 33-amino acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-terminal domain with features typical of a bacterial outer membrane protein. The VacA precursor shows no significant primary sequence homology with any previously reported protein, but its structural organization closely resembles the IgA protease-type of exoprotein produced by pathogenic Neisseriae and Haemophilus species. Our current data support a model for secretion of the cytotoxin through the two bacterial membranes which involves the 50 kDa domain for outer membrane translocation with subsequent proteolytic cleavage and release of the mature 87 kDa cytotoxin into the extracellular environment.
Mol Microbiol 1994 Apr
PMID:Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. 805 55

MnSOD is an antioxidant enzyme whose decrease in activity appears involved in tumorigenesis. We had previously reported the production of a monoclonal antibody, named 35.8, against rat MnSOD. In the present paper we show that it recognizes human and mouse MnSODs, although with different detection limits. We also use the antibody for immunofluorescence studies and observed that the antibody yields a positive staining of a non-nuclear protein, in rat and human organs where high concentration of MnSOD activity have been reported, and a lack of staining in rat kidney where MnSOD activity is decreased. Two tumors, an experimental rat hepatocarcinoma and a human liver metastasis from a gastrointestinal adenocarcinoma, are found negative for immunostaining.
Biochem Mol Biol Int 1994 May
PMID:Monoclonal antibody 35.8 recognizes human, mouse and rat MnSODs in western blot and immunostaining. 808 Dec

p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adenomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:p53 gene mutations in gastric adenomas. 809 76


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