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

Several studies have implicated the extracellular matrix-degrading metalloproteinases (MMPs) as essential agents in tumor cell invasion and metastasis. In the present study, we have investigated the patterns of expression of a number of MMPs and their specific tissue inhibitors (TIMP-1 and TIMP-2) in human colonic tissue samples that represent various stages of progression from adenomas showing different degrees of dysplasia to adenocarcinomas. We assessed levels of mRNA by Northern blot analysis and the results were measured semiquantitatively by densitometry. In total, we analyzed nine adenomas of varying size and with varying degrees of dysplasia, three adenomas with adenocarcinoma (malignant polyps), and five adenocarcinomas. Although expression of MMP and TIMP mRNA was highly intercorrelated, transcripts for stromelysin 3 and TIMP-2 (high) showed the strongest relation to the neoplastic process. Detection of stromelysin 3 mRNA accompanied a diagnosis of severe dysplasia or malignancy, whereas levels of TIMP-2 (high) mRNA transcripts permitted finer distinctions on the neoplastic continuum. These data indicate changes within extracellular matrix acquired during the process of malignant transformation of human sporadic colorectal neoplasia.
Diagn Mol Pathol 1993 Jun
PMID:Expression pattern of metalloproteinases and their inhibitors changes with the progression of human sporadic colorectal neoplasia. 826 81

We determined loss of heterozygosity from formalin-fixed, paraffin-embedded tissue of colorectal carcinoma using microsatellite polymorphism. The polymorphism was assayed based on DNA amplification by the polymerase chain reaction (PCR). The PCR-analyzed microsatellite method was applied to assay degraded DNA extracted from paraffin-embedded blocks with adenocarcinoma of colon. The DNA from 26 tumors as well as their corresponding normal tissue samples were successfully amplified using a dinucleotide microsatellite located within an intron of the deleted in colorectal carcinoma gene. Allele losses on this marker were detected in 33% of informative colorectal carcinomas. This study demonstrates that microsatellites provide a powerful set of DNA markers for loss of heterozygosity on archival specimens.
Diagn Mol Pathol 1993 Jun
PMID:Loss of heterozygosity detected in formalin-fixed, paraffin-embedded tissue of colorectal carcinoma using a microsatellite located within the deleted in colorectal carcinoma gene. 826 82

The new cell line PaTu 8902 was established from a human pancreatic grade II adenocarcinoma of ductal origin. In early passages, cultured cells showed a high degree of heterogeneity in terms of their morphology and the number of chromosomes per cell. When transplanted subcutaneously into nude mice, these cells grew as tumors with a similar morphology and differentiation (grade II) to the primary tumor. In contrast, after prolonged cultivation, cells were more homogenous in terms of their morphology and number of chromosomes per cell, and the corresponding nude mouse xenografts were less differentiated (grade III). When cells from late passages were injected intravenously into nude mice, lung metastases occurred after 3-4 weeks. In addition, tumor cells were found in the wall of the esophagus and in the pleural cavity, indicating a high metastatic potential for PaTu 8902 cells in nude mice.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Structural analysis of a new highly metastatic cell line PaTu 8902 from a primary human pancreatic adenocarcinoma. 828 16

Gastrin has been shown to promote the growth of some colonic tumor cell lines. To evaluate the involvement of this hormone in the proliferation of gastric tumors, we studied the effects of gastrin/CCK-receptor antagonists (L365,260 and L364,718), proglumide and C terminal-specific gastrin antibodies on the human gastric adenocarcinoma cell line HGT-1. L365,260, but not L364,718, dose-dependently inhibited cell proliferation (72% after 4 days at 10 nM) and [3H]thymidine incorporation (68% after 2 days at 10 nM) in serum-free medium. No cytotoxic effects of proglumide or L365,260 on this cell line were detected. Proglumide inhibited cell proliferation in serum-free medium (40% and 66.5% after 2 and 4 days of treatment; IC50 = 1.4 mM) and in 5% fetal calf serum (FCS)-supplemented medium (30% and 22% after 2 and 4 days of treatment; IC50 = 3.25 mM). [3H]Thymidine incorporation was also inhibited by proglumide in serum-free medium (IC50 = 2.3 mM) and 5% FCS-supplemented medium (IC50 = 3.35 mM). Gastrin did not induce cell proliferation or increase [3H]thymidine incorporation and no high-affinity gastrin binding sites were observed. However, C terminal-specific gastrin antibodies, even at low concentration, caused a dramatic decrease in both cell number (IC50 = 1:4000 antiserum dilution) and [3H]thymidine incorporation (IC50 = 1:400 antiserum dilution) in the HGT-1 cell line. In addition, immunofluorescence analysis revealed that these antibodies specifically bind HGT-1 cells and radioimmunoassay analysis confirms the presence of gastrin/CCK-like peptide in cell extracts.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 May
PMID:Evidence for autocrine growth stimulation by a gastrin/CCK-like peptide of the gastric cancer HGT-1 cell line. 831 31

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.
Mol Carcinog 1993
PMID:Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis. 835 90

Polymeric immunoglobulin receptor (pIg-R) is synthesized by epithelial cells lining the bronchial mucosa. It is released in secretions as free secretory component (SC) or bound to Ig as secretory Ig (S-IgA and S-IgM). To evaluate the usefulness of SC and pIg-R expression as tumour markers, we measured SC and secretory Ig, using enzyme-linked immunosorbent assay, in the serum of 45 patients with lung carcinomas, in the serum of 10 patients with non-neoplastic diseases, and in the serum of 45 control subjects. We also studied the immunohistochemical expression of pIg-R and its mRNA in tumors from 20 out of the 45 patients. Serum levels of SC and S-IgA were similarly and significantly elevated in patients with lung cancer (squamous cell carcinoma [25 cases], small cell carcinoma [7 cases], adenocarcinoma [13 cases]) and with non-neoplastic diseases, as compared with control subject levels (P < 0.001). The highest SC levels were found in patients with adenocarcinoma although the mean SC level was not different from other pathologic conditions. pIg-R was usually not detected in the cells of small cell carcinoma or of squamous cell carcinoma, whereas it was found in the cells of five adenocarcinomas and in the two in situ carcinomas under study. The specific mRNA analysis usually agreed with the immunolocalization of pIg-R. A single band at 3.8 kb was detected in the positive tumor tissues and in normal lung tissues. However, the signal was weak in one case of squamous carcinoma and stronger in two out of three adenocarcinomas, than in normal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Sep
PMID:Nonspecific increased serum levels of secretory component in lung tumors: relationship to the gene expression of the transmembrane receptor form. 839 72

Detection of the activity of beta-1,4-galactosyltransferase (beta-1,4-GT) in suspensions of viable mouse hepatocytes, the human hepatoma cell line Hep G2, the human colonic adenocarcinoma cell line HT-29, the monocyte-like cell line U937, and human splenic B and T lymphocytes suggested the presence of beta-1,4-GT, in an enzymatically active form, on plasma membranes. The presence of beta-1,4-GT on cell surfaces was also indicated from the effect of trypsinization of live cells, which significantly reduced cell surface beta-1,4-GT activity, but did not affect the activity associated with cytoplasmic membranes. Furthermore, the presence of beta-1,4-GT on the cell surface was demonstrated by indirect immunofluorescence staining of cells with anti-beta-1,4-GT antibody. The detection of radioactivity in immunoglobulins (Ig) and their component chains after incubation with suspensions of intact cells in the presence of Mn2+ and UDP-[3H]-galactose, indicated that Ig molecules were galactosylated. In the absence of UDP-[3H]-galactose, beta-1,4-GT on cell surfaces, or immobilized on Sepharose-4B, formed stable complexes with galactose acceptors, including Ig. The efficiency of binding decreased in the order: J chain > alpha chain > mu chain > polymeric IgA2 > monomeric/polymeric IgA1 > IgM > IgG. Thus, beta-1,4-GT could act as a cell-surface receptor for Ig through a cation-dependent, lectin-like association of the beta-1,4-GT with the carbohydrate moieties of the Ig. This was confirmed by indirect surface immunofluorescence and radiolabeled ligand binding assays. The binding was inhibitable by EDTA, alpha-lactalbumin (in the presence of glucose), GlcNAc, or uridine 3',5'dialdehyde. At 37 degrees C, the apparent affinity constants and association rate constants of interaction between cell surface beta-1,4-GT on glutaraldehyde-fixed HT-29 and U937 cells and alpha 2 chain or monomeric IgA1 were in the range from 7.1 x 10(7) to 4.6 x 10(8) M-1 and from 1 x 10(5) to 3 x 10(6) M-1 s-1, respectively. The dissociation rate constants and half time of dissociation calculated from these data were in the range from 2.1 x 10(-2) to 5.0 x 10(-4) s-1 and from 33 to 1380 s, respectively. The number of alpha 2 or IgA1 molecules bound per HT-29 and U937 cell were in the range from 1.9 x 10(5) to 1.3 x 10(6). The binding of IgA by the cell surface beta-1,4-GT was not associated with internalization or the catabolic degradation of the ligand.
Mol Immunol 1993 Feb
PMID:Interactions of cell-surface galactosyltransferase with immunoglobulins. 843 5

The High Mobility Group protein HMG 17 has been isolated from human leukemia cells obtained from patients with chronic myelogenic leukemia (CML). The level of expression of HMG 17 was investigated Human leukemia cells have three times more HMG 17 than normal human leukocytes. Three other malignant tissues were also compared. Two of these breast adenocarcinoma and other intestine- also exhibit higher amounts of HMG 17. The elevated expression of HMG 17 suggests that the level of the protein may be associated with rates of cellular proliferation.
Biochem Mol Biol Int 1995 Jul
PMID:Elevated levels of the chromosomal protein HMG 17 in chronic myelogenic leukemia. 852 42

We compare testosterone (T) metabolism in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH) and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts, respectively. Northern blot analysis of total RNA from epithelial cells (BPH or adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1 isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts, only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) and finasteride, inhibited DHT formation with a preferential action of 4-MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon) inhibited the formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and fibroblasts, respectively]. These results have important therapeutic implications when selecting appropriate treatment options for BPH.
J Steroid Biochem Mol Biol 1995 Dec
PMID:Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts. 854 Dec 34

A polymerase chain reaction strategy was utilized to identify members of the cadherin family of cell adhesion molecules that are expressed in normal human colon and colon carcinoma. E-cadherin (an epithelial cadherin) and OB-cadherin (a mesenchymal cadherin) were found to be present in the colon specimens. Furthermore, a novel semiquantitative polymerase chain reaction (PCR) assay was developed for each of these two cadherins. These assays were used to determine the relative levels of E-cadherin and OB-cadherin in normal human colon and colon carcinoma specimens. E-cadherin levels were found to be reduced approximately twofold in the adenocarcinoma specimens in comparison to matched normal colon specimens. In contrast, OB-cadherin levels did not correlate with malignant transformation. We speculate that this novel PCR method will be widely applicable for assessing E-cadherin mRNA levels in carcinomas.
Exp Mol Pathol 1995 Apr
PMID:E-cadherin and OB-cadherin mRNA levels in normal human colon and colon carcinoma. 854 95


<< Previous 1 2 3 4 5 6 7 8 9 10