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)

To study the regulation of mucin synthesis in canine tracheal epithelial cells, it is desirable to establish a cell line which synthesizes mucin continuously. We adopted the approach of immortalizing canine tracheal epithelial cells using a vector encoding the human papillomavirus (type 18) E6 and E7 genes. The E6 and E7 genes are essential and sufficient for the immortalization of human genital keratinocytes, as well as human tracheal epithelium. Primary epithelial cells from dog trachea were transfected with a vector containing HPV18 genes E6 and E7. The resultant cells (CT1) were cloned and maintained in selective medium supplemented with growth factors and hormones. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated the expression of the canine tracheal mucin (CTM) mRNA in these cells. The half-life of the CTM mRNA was found to be 45-60 min. Incorporation of labelled precursor (glucosamine) indicated that high-molecular-weight mucin glycoprotein was synthesized by these immortalized cells, which reacted with the antiserum to the native CTM. Equilibrium gradient centrifugation analysis showed that the buoyant density of the mucin synthesized in CT1 cells (1.486 g/ml) was similar to the reported value for native CTM (1.5 g/ml). Mucin which was isolated from immortalized cells was not a proteoglycan as chondroitinase treatment had no effect. These results suggest that CT1 cells synthesize a mucin glycoprotein which exhibits properties similar to native CTM. When characterized by immunostaining with a pool of monoclonal antibodies, these cells showed common epithelial antigens related to keratin expression. The CT1 cell line represents a unique resource for studying mucin biosynthesis and regulation.
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PMID:Mucin synthesis in immortalized canine tracheal epithelial cells. 773 45

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44. Reverse transcriptase polymerase chain reaction analysis was used to map the temporal regulation of specific CD44 variant isoforms. In each age group, hyaluronan was localized exclusively in the stromal matrix. Hyaluronan was greatly reduced in the later ages and was entirely absent around the developmentally quiescent proximal regions of the ducts. Early in prostate development, CD44 was prominent in the mesenchyme. However, in the later phases, CD44 expression became associated with membranes of epithelial cells. The role of hyaluronan-CD44 interactions in ductal branching morphogenesis was studied by serum-free organ culture of mouse anterior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis. Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching morphogenesis. These results are suggestive of the significant role played by hyaluronan-CD44 interactions in mediating androgen-induced prostatic growth and morphogenesis.
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PMID:Hyaluronan is a prerequisite for ductal branching morphogenesis. 937 96

We have examined the catabolism of the proteoglycans aggrecan, decorin and biglycan in fresh tendon samples and in explant cultures of tissue from the tensional and compressed regions of young and mature bovine tendons. A panel of well-characterized antibodies that recognize glycosaminoglycan or protein (linear or neoepitope) sequences was used to detect proteoglycans and proteoglycan degradation products that were both retained within the tissue and released into the culture medium. In addition, a reverse-transcriptase-mediated PCR analysis was used to examine the mRNA expression patterns of tendon proteoglycans and aggrecanases. The results of this study indicate a major role for aggrecanase(s) in the catabolism of aggrecan in bovine tendon. The study also provides a characterization of glycosaminoglycan epitopes associated with the proteoglycans of tendon, illustrating age-related changes in the isomers of chondroitin sulphate disaccharides that remain attached to the core protein glycosaminoglycan linkage region after digestion with chondroitinase ABC. Evidence for a rapid turnover of the small proteoglycans decorin and biglycan was also observed, indicating additional molecular pathways that might compromise the integrity of the collagen matrix and potentially contribute to tendon dysfunction after injury and during disease.
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PMID:Catabolism of aggrecan, decorin and biglycan in tendon. 1092 42

Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in 11 HNSCC patients (2841 +/- 887 ng/mg protein) when compared to 6 normal controls (579.3 +/- 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 +/- 1.4 mU/mg protein) when compared to normal controls (2.8 +/- 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a approximately 55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.
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PMID:Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. 1499 92