Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Very late antigen-4 (VLA-4) composed of alpha 4 and beta 1, a member of the beta 1-integrin subfamily, facilitates cell-to-cell interaction with vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells (EC). Attachment of blood-borne tumor cells to EC is a crucial step for hematogenous metastasis, and VLA-4-positive tumor cells can attach to EC by binding to VCAM-1. Renal-cell cancer (RCC) reveals proportionally greater percentages of metastases than other carcinomas at initial diagnosis. We investigated whether VLA-4 is expressed on RCC, and how such expression on RCC correlates with the metastatic potential of RCC. Immunohistochemical staining on 66 primary and 4 metastatic RCC showed that 4 out of 4 metastatic and 5 out of 8 primary RCC from patients with lung and/or brain metastases expressed alpha 4 and beta 1 chains. On the other hand, 13 of 58 RCC without metastases expressed alpha 4 chain, alpha 4 and beta 1 expressions were also detected on 5 out of 5 human RCC cell lines, ACHN, KRC/Y, A498, Caki1 and Caki2, by flow-cytometric analysis. Reverse-transcriptase-polymerase-chain-reaction (RT-PCR), followed by Southern-blot hybridization with cDNA probe for a alpha 4 chain, also confirmed mRNA production in 4 out of 5 RCC cell lines. Furthermore, adhesion of alpha 4-positive RCC cell lines to human umbilical-vein endothelial cells (HUVEC) was augmented by treatment of HUVEC with tumor necrosis factor-alpha (TNF-alpha). This adhesion was inhibited by anti-alpha 4 or anti-VCAM-1 antibodies, suggesting that VLA-4-VCAM-1 interaction was involved in the adhesion between RCC cells and HUVEC. Taken together, VLA-4 on RCC cells might play a crucial role in their hematogenous metastasis.
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PMID:Possible significance of VLA-4 (alpha 4 beta 1) for hematogenous metastasis of renal-cell cancer. 789 40

This study aimed to establish patterns of cellular fibronectin mRNA splice variants in normal oral mucosa, oral squamous cell carcinoma, oral leukoplakias with and without atypia, and focal reactive overgrowths of oral mucosa. Particular emphasis was placed on evaluation of either the EDA or EDB domains as markers of malignancy. Total RNA was extracted from normal oral mucosa, oral squamous cell carcinoma, oral leukoplakias with and without atypia, reactive epulides, fibroepithelial polyps and denture-related hyperplasia. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to identify different fibronectin transcripts at three splice sites (EDA, EDB and IIICS). All the tissues investigated produced EDA+, EDA-, EDB+ and EDB- splice variants, and this study did not support RT-PCR-based detection of either EDA or EDB domains as markers of malignancy in oral tissues. Variations in IIICS splice patterns were observed, although these were not specific to any lesion group. In particular, there were differences in either the inclusion or omission of the domain coding for the CS-5 binding site for alpha 4 beta 1 integrin, whereas the CS-1 binding site for alpha 4 beta 1 integrin was typically present when additional domains were included at the IIICS splice site. In conclusion, complex patterns of fibronectin splice variant transcripts exist in normal and pathological oral mucosa. This may reflect the multiple biological functions identified for fibronectin proteins, although the significance of different specific fibronectin splice variants has yet to be fully elucidated.
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PMID:RT-PCR investigation of fibronectin mRNA isoforms in malignant, normal and reactive oral mucosa. 930 23

The futb gene, which encodes the first bovine alpha 3-fucosyltransferase described, consists of five exons (a, b, c, d, and e), the first four being located upstream of the coding exon e. Together with the four introns (i1, i2, i3, and i4) they span a DNA genomic sequence of about 10 kb. futb is expressed as four tissue-specific transcripts differing by their 5'-untranslated (5'-UT) regions, but only one transcript includes all exons, while the other three begin at internal sites of exon c. A short sequence of the latter is homologous to distinct 5'-UT exons of FUT6 (alpha 3-fucosylation) and FUT3 (alpha 4-fucosylation), two human genes whose coding sequences are homologous to coding exon e of futb. Upstream and downstream, the exon c intronic regions of the bovine gene are homologous to 5'-UT exons of human FUT3 (exon B) and FUT6 (exons A, B, and C). Thus, exon c appears to be the most ancestral 5'-UT exon known among these alpha 3-fucosyltransferase genes. Interestingly, distribution of short interspersed nuclear elements in the i3 intron adjacent to exon c reveals that two repeat sequences are joined to form a reverse-transcriptase-like encoding sequence highly homologous to an open reading frame located at the 3' end of the bovine gamma globin gene. This organization suggests that duplication events that have generated the primate FUT3-FUT5-FUT6 cluster might have occurred through a long-interspersed-nuclear-element-based mechanism of unequal crossing over, as described for the globin cluster. Complete organization of the bovine futb gene reveals that in addition to duplication events, the lineage leading to primate FUT3, FUT5, and FUT6 genes results from rearrangements of intronic sequences which have created for each new gene specific regulatory 5'-UT exonic sequences.
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PMID:Complete genomic organization of futb encoding a bovine alpha 3-fucosyltransferase: exons in human orthologous genes emerged from ancestral intronic sequences. 1055 85

hCG has been reported to cause an inflammation-like effect in the testis, although the background and consequences of this phenomenon remain to be understood. This investigation reveals that a single injection of hCG (100 U) induces a transient surge in pro-inflammatory cytokine expression in the adult rat testis. Reverse transcriptase PCR analysis demonstrated onset of testicular expression of IL-1beta and IL-6 mRNA and increases in the levels of mRNA encoding the constitutively expressed cytokines IL-1alpha, IL-1 receptor antagonist, and tumor necrosis factor-alpha 4 h after hCG injection and a maximal response after 8-12 h. These increases were accompanied by a transient increase in testicular IL-1 bioactive protein. Twenty-four hours after administration of hCG, the levels of all cytokine mRNA had decreased, although most were still elevated above control. Immunohistochemical staining revealed that the IL-1beta protein was undetectable in normal testes but was seen to be localized to interstitial macrophages but not Leydig cells after hCG treatment. Testes devoid of Leydig cells after pretreatment with ethane dimethane sulphonate exhibited normal staining for interstitial macrophages but failed to respond to hCG with increases in IL-1beta mRNA and protein expression. We conclude that hCG induces testicular inflammation via local activation by Leydig cells of the production of pro-inflammatory cytokines by resident macrophages. It remains to be investigated whether the high-dose hCG regimens used for treatment of boys with cryptorchidism could induce similar increases of pro-inflammatory cytokines in the human testis and if such treatments could adversely affect future testicular function.
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PMID:Single subcutaneous administration of chorionic gonadotropin to rats induces a rapid and transient increase in testicular expression of pro-inflammatory cytokines. 1584 39