Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Squamous cell carcinomas of the head and neck are known for their aggressive growth and propensity to metastasize. Invasion is facilitated by matrix metalloproteineases (MMPs). Tissue inhibitors of MMPs (TIMPs) negatively regulate MMP activity. MMP and TIMP expression in head and neck squamous cell carcinomas was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). qRT-PCR allows measurement of several mRNAs from as little as 4 microg of total cellular RNA. We measured MMP-1, MMP-2, MMP-9, and TIMP-1 expression in 8 specimens of primary tumors and adjacent normal tissue. MMP-1 was overexpressed in 6 of 8 tumors, and MMP-9 was overexpressed in 4 of 7 tumors. MMP-2 was expressed in 3 of 8 tumors and 3 of 8 normal samples. TIMP-1 was expressed in all specimens. This work demonstrates that qRT-PCR can be used to examine expression of specific mRNAs in clinical specimens. Therefore this method provides another tool for the molecular analysis of tumors.
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PMID:Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in laryngeal and pharyngeal squamous cell carcinoma: A quantitative analysis. 1079 52

Epidemiologic studies have indicated the association between tobacco smoking and skin aging, but the exact mechanism of tobacco smoke-induced premature skin aging is currently unknown. In this study, we investigated the alterations of collagen, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human fibroblasts treated with tobacco smoke extract. Human fibroblasts were exposed to different concentrations of water-soluble extract from tobacco smoke. Human fibroblasts irradiated with ultraviolet A1 (UVA1) were used as positive controls because the mechanism of UVA1-mediated MMP expression has been well characterized. The expression of MMP and TIMP was analyzed semiquantitatively following reverse transcriptase-polymerase chain reaction. Production of type I and type III collagens was detected by Western blotting and biosynthesis of new collagen was assessed by 3H-proline incorporation. Upon treatment with tobacco smoke extract or UVA1 irradiation, the expression of MMP-1 and MMP-3 mRNA was significantly increased in a dose-dependent manner. Maximum induction was observed with 25 microl/ml tobacco smoke extract. In contrast, the expression of TIMP-1 and TIMP-3 mRNA remained unchanged. Western blotting of the supernatant revealed that type I and type III collagens were decreased as compared with untreated controls. Collagen biosynthesis was significantly reduced by 40.1% following treatment with 25 microl/ml tobacco smoke extract. Sodium azide, L-ascorbic acid and Trolox (a water-soluble vitamin E) prevented both the UVA1- and the tobacco-induced alteration of MMP-1. These observations suggest that the imbalance of connective tissue matrix components might contribute to the molecular basis for premature skin aging in smokers. They also suggest that reactive oxygen species including singlet oxygen mediate this process.
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PMID:Alterations of extracellular matrix induced by tobacco smoke extract. 1083 12

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an inhibitor of matrix metalloproteinase (MMP) in human carcinomas. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. On the other hand, recent reports have disclosed that TIMP-1 also possesses a growth-promoting function. The clinical significance of TIMP-1 expression has not been fully determined in breast carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor tissues of 100 breast carcinoma cases by a reverse transcriptase-polymerase chain reaction assay. The expression of TIMP-1 mRNA in each case was evaluated semi-quantitatively with adjustment for the TIMP-1 expression in a control breast carcinoma cell line, MCF7. There was a significant inverse correlation between the TIMP-1 expression and lymph node metastasis (p<0.05). A multivariate analysis disclosed that TIMP-1 expression status was an independent determinant factor for lymph node metastasis. In addition, the tumors with positive estrogen or progesterone receptors showed a higher TIMP-1 mRNA expression than those without the receptors, but this did not reach statistical significance. The findings suggest that the breast tumors with high TIMP-1 expression might show less malignant potential than those with low TIMP-1 expression.
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PMID:Expression of tissue inhibitor of matrix metalloproteinase-1 in human breast carcinoma. 1085 60

There is a growing body of evidence that implicates matrix metalloproteinases (MMPs) as major players in numerous diseased conditions. The articular cartilage degradation that is characteristic of rheumatoid arthritis (RA) is believed to be mediated by the collagenase subfamily of matrix metalloproteinases. The preference of collagenase-3 (CL-3) for collagen type II makes it a likely candidate in the turnover of articular cartilage and a potential target for drug development. In this study, RA synovial membrane tissue was shown to express CL-3 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and protein by immunohistochemistry. Fibroblasts isolated and cultured from RA synovial membrane tissue were induced to express CL-3 mRNA. CL-3 mRNA was detected after PMA treatment in 16 of the 18 RA synovial membrane fibroblast cell lines established for this study. These fibroblasts also expressed mRNA for collagenase-1 (CL-1, MMP-1), membrane type-1 matrix metalloproteinase, gelatinase A, gelatinase B, stromelysin-1, stromelysin-2, TIMP-1, and TIMP-2. They were further shown to express CL-1 mRNA constitutively and CL-3 mRNA only after stimulation with PMA, IL-1, TGF-beta1, TNF-alpha, or IL-6 with IL-6sR. These fibroblasts also expressed after induction both CL-1 and CL-3 at the protein level as determined by Western blot analyses and immunofluorescence.
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PMID:Induction of collagenase-3 (MMP-13) in rheumatoid arthritis synovial fibroblasts. 1104 Apr 55

Stromelysin-2 is a matrix metalloproteinase that degrades in vitro several protein components relevant to wound repair such as collagens III and IV, gelatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix metalloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large variety of wounds (normally healing dermal and mucosal wounds, suction blisters, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to stromelysin-2 expression and how it is induced in relation to other matrix metalloproteinases. Our results show that stromelysin-2 mRNA and protein are upregulated later (at 3 d) than matrix metalloproteinase-1 in normally healing wounds and ex vivo explants, in which stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing stromelysin-2 was greatest in chronic inflamed diabetic and venous ulcers compared with rheumatoid and decubitus ulcers, six of which had no signal. In keratinocyte cultures, tumor necrosis factor-alpha, epidermal growth factor, and transforming growth factor-beta1 induced stromelysin-2 expression as measured by quantitative reverse transcriptase-polymerase chain reaction, whereas different matrices did not upregulate the mRNA. Immunostaining demonstrated stromal transforming growth factor-beta1 in contact with the stromelysin-2-positive keratinocytes. Our results suggest that stromelysin-2 expression is important for the normal repair process and is upregulated by cytokines rather than cell-matrix interactions. Stromelysin-2 is most likely to participate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing.
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PMID:Stromelysin-2 is upregulated during normal wound repair and is induced by cytokines. 1106 14

Neoplastically transformed mouse and human keratinocytes elevate transactivation of both activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) transcription factors. The present study addresses the question of whether elevated NFkappaB in addition to elevated AP-1-dependent gene expression is necessary for maintaining the tumor cell phenotype. When a tetracycline-regulatable dominant-negative c-jun (TAM67, having a truncated transactivation domain) was expressed in tumorigenic human keratinocytes, AP-1- and NFkappaB- but not p53-dependent reporter activity was inhibited by 40-60%. Tumor phenotype, as measured by anchorage-independent growth, was inhibited by 90%. Neither AP-1/NFkappaB activation nor expression of tumor phenotype was inhibited in TAM67-harboring keratinocytes under noninducing conditions. Electrophoretic mobility shift analysis showed that induction of TAM67 expression slightly increased AP-1- but reduced NFkappaB DNA-binding activity. Immunoprecipitation showed that TAM67 interacted in keratinocyte nuclei with NFkappaB p65, suggesting that inhibition of NFkappaB by TAM67 is mediated by direct protein-protein interactions, possibly producing decreased binding to DNA or inactivating p65. To analyze the putative effector genes that may be targeted by TAM67, expression of genes responsive to AP-1 or NFkappaB was measured by reverse transcriptase-polymerase chain reaction in TAM67 transfectants with or without TAM67 induction. Induction of TAM67 inhibited or reduced the expression of collagenase I, stromelysin I (AP-1 responsive), and interleukins 1 and 6 (NFkappaB responsive). These results indicate that genes controlled by NFkappaB and by AP-1 may be transformation-relevant targets of TAM67 and that TAM67 may inhibit NFkappaB activation through direct interaction with NFkappaB p65. Moreover, the findings provide proof for the principle of using inducible TAM67 as a gene therapy to suppress tumor phenotype in human carcinoma cells.
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PMID:Induced expression of dominant-negative c-jun downregulates NFkappaB and AP-1 target genes and suppresses tumor phenotype in human keratinocytes. 1110 61

Cell-cell contact of myeloma-derived cell lines (MDCL) or fresh myeloma cells with bone marrow stromal cells (BMSC) is known to induce interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) production by a marrow stromal cell line. To determine if other BMSC transcripts are altered during cell-cell contact between BMSC and tumor cells, we have used cell lines ARH77 and U266 in an in vitro model. Using mRNA differential display and reverse transcriptase-polymerase chain reaction (RT-PCR), it was determined that a total of 141 transcripts were either upregulated or downregulated in the BMSC on contact with cell membrane from cell lines ARH77 and U266. Induction of two of these transcripts, interleukin-6 (IL-6) and gp130 in the BMSC by ARH77 cell membranes was studied in greater detail. Real-time PCR was used to quantitate transcript levels of gp130, IL-6, and 36b4, a housekeeping gene. Cycloheximide (CHX) alone increased both gp130 and IL-6 transcripts in the BMSC. In addition, CHX caused a superinduction of these transcripts in BMSC exposed to ARH77 cell membranes. The induction of gp130 was independent of the increase in IL-6 mRNA. Upregulation of gp130, a component of the membrane receptors for the IL-6 superfamily, can have profound effects on the response of BMSC to the IL-6 superfamily of cytokines.
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PMID:Acute activation of gp130 gene expression in bone marrow stromal cells by contact with myeloma-derived lymphoblastic cell line ARH77 cell membranes. 1133 Oct 38

Basaloid squamous carcinoma (BSC) is an uncommon aggressive variant of squamous cell carcinoma (SCC) with a predilection for the head and neck. In the English literature, approximately 40 cases of BSC in the oral cavity have been described. In this study, the clinicopathologic features of 2 cases of BSC affecting the buccal mucosa are reported. In addition, we compare the proliferative and invasive potential of BSC cells with that of poorly differentiated SCC cells matched for age, sex, site, and TNM status. Proliferative activity was studied through use of the argyrophilic nuclear organizer region (AgNOR) method and immunohistochemical quantification of proliferating cell nuclear antigen (PCNA). The invasive potential was evaluated through use of the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for matrix metalloproteinases (MMPs). Alterations of p53 were also investigated through use of immunohistochemistry. The tumors showed many clinical and histopathologic similarities to tumors in cases previously reported. The AgNOR and PCNA indices were significantly higher in the 2 cases of BSC than in the cases of SCC. Immunostaining for p53 protein showed a higher percentage of positive cells and more intense staining in the BSC tissues than in the SCC tissues. RT-PCR studies clearly demonstrated that the expression of MMP-1, MMP-2, and MMP-9 was higher in cells from BSCs than in cells from SCCs. Taken together, the data described here are compatible with the concept that BSC has a more aggressive biologic behavior than conventional SCC.
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PMID:Basaloid squamous carcinoma of the oral cavity: report of 2 cases and study of AgNOR, PCNA, p53, and MMP expression. 1134 36

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by fibroblast proliferation and extracellular matrix accumulation. However, studies on fibroblast growth rate and collagen synthesis have given contradictory results. Here we analyzed fibroblast growth rate by a formazan-based chromogenic assay; fibroblast apoptosis by in situ end labeling (ISEL) and propidium iodide staining; percent of alpha-smooth muscle actin (alpha-SMA) positive cells by fluorescence-activated cell sorter; and alpha1-(I) collagen, transforming growth factor (TGF)-beta1, collagenase-1, gelatinases A and B, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, and -4 expression by reverse transcriptase/polymerase chain reaction in fibroblasts derived from IPF and control lungs. Growth rate was significantly lower in IPF fibroblasts compared with controls (13.3 +/- 38.5% versus 294.6 +/- 57%, P < 0.0001 at 13 d). Conversely, a significantly higher percentage of apoptotic cells was observed in IPF-derived fibroblasts (ISEL: 31.9 +/- 7.0% versus 15.5 +/- 7.6% from controls; P < 0.008). alpha-SMA analysis revealed a significantly higher percentage of myofibroblasts in IPF samples (62.8 +/- 25.2% versus 14.8 +/- 11.7% from controls; P < 0.01). IPF fibroblasts were characterized by an increase in pro-alpha1-(I) collagen, TGF-beta1, gelatinase B, and all TIMPs' gene expression, whereas collagenase-1 and gelatinase A expression showed no differences. These results suggest that fibroblasts from IPF exhibit a profibrotic secretory phenotype, with lower growth rate and increased spontaneous apoptosis.
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PMID:Fibroblasts from idiopathic pulmonary fibrosis and normal lungs differ in growth rate, apoptosis, and tissue inhibitor of metalloproteinases expression. 1135 Aug 29

Matrix metalloproteinases (MMPs) collectively degrade extracellular matrix and basement membrane proteins in chronic inflammation and bone-destructive lesions. This study examined the ability of immunoglobulin-producing plasma cells, typically present in sites of chronic inflammation, to express collagenases (MMP-8 and -13) in vivo and in vitro. Phorbol-12-myristate-13-acetate, interleukin-6, and tumour necrosis factor-alpha and heparin with the tumour promoter or cytokines potently enhanced (up to nine-fold) MMP-8 and -13 expression by the RPMI 8226 myeloma cell line, as evidenced by western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemical analysis and in situ hybridization revealed that plasma cells expressed MMP-8 and -13 focally in periapical granulomas, odontogenic cysts, and malignant plasmacytomas. MMP-8 and MMP-13 from plasma cells can participate in bone organic matrix destruction at sites of chronic inflammation and neoplastic growth. Since MMP-13 was more frequently expressed than MMP-8 in plasma cells of strongly recurring keratocysts and malignant plasmacytomas, it is concluded that plasma cell MMP-13 has a particularly important role in benign and malignant bone-destructive lesions.
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PMID:Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions. 1140 Jan 51


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