Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gelatinase B is a regulated matrix metalloproteinase with important role in the remodeling of extracellular matrix and many pathological conditions such as tumor invasion and rheumatoid arthritis, physiological processes including embryonic growth and development, migration of blood leukocytes into tissues and tissue remodeling. Elevated levels of certain MMPs are believed to be associated with various pathological states. We cloned the 5'-flanking 600 bp sequence of human gelatinase B gene by PCR, which controls the expression of the gene by ligating it to the chloramphenicol acetyltransferase gene. Four kinds of cell lines were used to transiently transfect. Deletion analysis revealed that 100 bp (-600 to -500 bp) contributed positively to induction by tumour necrosis factor. The 100 bp contains NF-kappa B site, Ap-1 site, PEA3 and Sp-1 site. The expression of the human gelatinase B gene varied in different cells in the presence of TNF.NF-kappa B factor may play an important role in regulating the gene expression. Comparison of the finding with those for the promoter of gelatinase A, collagenase and stromelysin shows that the determinant for the inducibility of the gelatinase B gene is more complex.
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PMID:Molecular mechanism of transcriptional activation of human gelatinase B by proximal promoter. 884 71

Expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential. Moreover, UV-B irradiation of primary cutaneous melanoma cells induces IL-8 mRNA and protein production and increases both tumor growth and metastasis in nude mice. Although IL-8 has been shown to be an angiogenic factor, the biological consequences of increased IL-8 production by melanoma cells and the role of IL-8 in the metastatic process remains unclear. The purpose of this study was to determine the role of IL-8 in tumor growth and metastasis of human melanoma cells. Nonmetastatic SB-2 melanoma cells with negligible levels of IL-8 were transfected with IL-8 cDNA and subsequently analyzed for changes in their tumorigenic and metastatic potential. Enforced expression of IL-8 rendered the melanoma cells highly tumorigenic and increased their metastatic potential as compared with parental and control transfected cells. The IL-8-transfected cells displayed up-regulation in M(r) 72,000 collagenase type IV (MMP-2) mRNA and collagenase activity and increased invasiveness through Matrigel-coated filters. Moreover, when the MMP-2 promoter was linked upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, CAT activity was up-regulated in IL-8 but not in control transfected cells, suggesting that IL-8 is involved in MMP-2 gene transcription. Activation of type IV collagenase by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis.
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PMID:Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. 932 44