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)

The presence of mRNA for epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) was demonstrated in small fragments of human endometrium and decidua by use of the technique of reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. The presence of mRNA encoding EGF and TGF alpha has not been shown in human endometrium previously. Other studies using conventional techniques, such as Northern blot or in-situ hybridization, showed the presence in low copy number of EGF but not TGF alpha in murine endometrium. Messenger RNA for EGF was not present in peripheral leukocytes or platelets, suggesting an endometrial source for the message. Messenger RNA for TGF alpha was found in these blood components, thus preventing confirmation of the source of TGF alpha mRNA.
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PMID:Identification of mRNA for epidermal growth factor and transforming growth factor-alpha present in low copy number in human endometrium and decidua using reverse transcriptase-polymerase chain reaction. 171 8

The study presented here was designed to further investigate the role of transforming growth factor-alpha (TGF alpha) in skin tumor promotion by examining the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and several non-phorbol ester promoters to alter TGF alpha mRNA and protein levels in mouse epidermis. Total RNA was isolated from SENCAR mouse epidermis at various times after single topical treatments with TPA (3.4 nmol), chrysarobin (220 nmol), okadaic acid (2.5 nmol), and thapsigargin (8.5 nmol). Northern analyses of these isolated RNA samples revealed that all four tumor promoters transiently elevated TGF alpha mRNA levels. Whereas TPA, okadaic acid, and thapsigarin elevated TGF alpha mRNA levels over similar time courses (peak at 4-8 h), chrysarobin elevated TGF alpha mRNA levels with a markedly delayed time course (peak at 24-48 h). More detailed studies with TPA also revealed that multiple treatments (four over a 2-wk period) transiently elevated TGF alpha mRNA in both the epidermis and the dermis. The time courses for changes in TGF alpha mRNA after multiple TPA treatments were similar for both tissues. To facilitate studies of altered TGF alpha mRNA expression in mouse epidermis and possibly other mouse tissues, a semiquantitative reverse transcriptase-polymerase chain reaction method was developed. This method faithfully revealed changes in TGF alpha mRNA levels with all four tumor-promoting agents similar to those determined by northern blot analyses. Immunofluorescence analysis of frozen sections from promoter-treated skin revealed elevated TGF alpha protein levels in both epidermis and dermis, although staining was most intense in the epidermal layer. Immunofluorescence analysis of epidermal hyperplasia adjacent to a full-thickness wound also demonstrated significant epidermal TGF alpha staining. Collectively, these results indicate that mechanistically diverse tumor promoter stimuli elevate TGF alpha mRNA and protein in SENCAR mouse epidermis. Elevated levels of TGF alpha may play an essential role in mitogenic stimulation during tumor promotion by diverse promoting stimuli.
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PMID:Elevation of transforming growth factor-alpha mRNA and protein expression by diverse tumor promoters in SENCAR mouse epidermis. 772 44

Transgenic female mice bearing human transforming growth factor-alpha (TGF alpha) cDNA under the control of the mouse mammary tumor virus enhancer/promoter became pregnant but failed lactation. TGF alpha mRNA was detected in the mammary glands of these mice by the reverse transcriptase-polymerase chain reaction. By the use of collagenase-dissociated mammary epithelial cells, the binding of prolactin to its receptor was determined before and after parturition. At the end of pregnancy, the binding in TGF alpha transgenic (TGF alpha [+]) mice was small and its amount was comparable to that in the TGF alpha negative (TGF alpha [-]) mice. On the day of parturition, prolactin binding in TGF alpha (+) mice increased approximately 1.9-fold (insignificant), while that in TGF alpha (-) mice elevated over 5.3-fold (P < 0.01). The binding sites per cell were also higher in TGF alpha (-)mice. Radioimmunoassay of prolactin suggested that in TGF alpha (+) mice the low level of prolactin binding after parturition was not due to masking effect of serum prolactin. Among six TGF alpha (+) mice assayed, one mother with the highest prolactin binding activity (3.7-fold increase) initiated lactation, but the others did not. As there was little difference between groups in the growth and synthesis in the mammary glands, it was concluded that the failure of lactation in TGF alpha (+) mice is principally due to the lack of elevation of mammary prolactin receptor after parturition. At present, the role of TGF alpha in this process is obscure; however, TGF alpha was revealed not to interfere with the binding of prolactin to the receptor.
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PMID:Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor alpha transgenic mice. 817 Oct 44

Human parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.
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PMID:Alterations in the level of phosphotyrosine signal transduction constituents in human parotid tumors. 863 6

Olfactory receptor neurons are continuously replaced postnatally through the initiation of the division and terminal differentiation of progenitor cells located in the basal layer of the olfactory epithelium. Although the factors that regulate this process in vivo are not known, recent in vitro studies demonstrated that members of the epidermal growth factor (EGF) family including transforming growth factor-alpha (TGF alpha) and EGF are highly potent in promoting the proliferation of progenitor cells, suggesting a role for the EGF receptor (EGFR), which is the molecular receptor for both mitogens. We have examined the expression of EGFR mRNA and protein in the olfactory epithelium by using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis and have examined their cellular localization with in situ RT-PCR and immunocytochemistry. RT-PCR and Southern blot analysis demonstrated that EGFR mRNA is expressed in the olfactory mucosa and also in the positive control tissues, kidney and tongue. The 170-kDa EGFR protein was identified with Western blot analysis in the olfactory epithelium and control tissues. Our results using in situ RT-PCR localized EGFR mRNA-expressing cells more extensively in the basal cell layer of the epithelium than did the immunocytochemical methods. These results suggest that EGFR mediates the mitogenic effect of TGF alpha and/or EGF on the quiescent basal cells to initiate the cell cycle.
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PMID:Epidermal growth factor receptor mRNA and protein are expressed in progenitor cells of the olfactory epithelium. 888 29

The growth and differentiation of olfactory sensory neurons are regulated tightly. We had shown previously, by immunohistochemistry, that transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor are present in the olfactory epithelium of untreated adult rats and that TGF-alpha is a potent mitogen of olfactory epithelium in vitro. Expression of EGF receptor and TGF-alpha was detected primarily in horizontal basal cells and supporting cells but rarely in globose basal cells, which suggested that EGF receptor is not a likely candidate for the mitotic regulator of sensory neurons. In order to expand the search for candidate regulators, we have now examined other members of the EGF family of receptors and ligands. By utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) methodology, we have detected the messenger RNA encoding the protein of the neu gene (p185neu) and Neu differentiation factor (NDF) isoforms in the olfactory mucosa. Immunohistochemical localization of p185neu and NDF indicates expression of these proteins in the olfactory epithelium of adult rats in regions where globose basal cells and immature sensory neurons are found, as well as in the ensheathing cells of the olfactory nerve. The presence of neu and NDF transcripts in the olfactory tissue and the localization of their encoded polypeptides to proliferative regions of the epithelium suggest involvement of these gene products in the regulated proliferation/differntiation of the sensory neurons.
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PMID:Expression of neu and Neu differentiation factor in the olfactory mucosa of rat. 901 Jul 26

Cytokines appear to play an important role in the development and progression of epithelial tumors. Cultured normal human thyroid follicular cells constitutively release high levels of interleukin-6 (IL-6) and IL-8, together with low to moderate levels of transforming growth factor-alpha (TGF-alpha) and TGF-beta. IL-6 appears to play multiple functions in thyroid physiology and disease. Because certain data indicate an inverse relationship between IL-6 production and epithelial tumor aggressiveness, we used both tissue culture methods and histochemical techniques to search for possible alterations of cytokine expression in thyroid carcinomas. As compared to cultures from normal tissue and well-differentiated carcinoma, production of IL-6 was strongly down-regulated in cultures derived from undifferentiated carcinoma. In contrast, levels of IL-8, TGF-alpha, and TGF-beta produced by neoplastic TFC were similar to those produced by normal cells. Actually, production of TGF-alpha was slightly enhanced in cultures from well-differentiated carcinoma. Immunoassay results were confirmed by reverse transcriptase-PCR analysis. Immunohistochemistry of human thyroid carcinomas (n = 99) and normal thyroid tissue (n = 85) showed that immunoreactive IL-6 was strongly diminished in undifferentiated forms (n = 34) and slightly reduced in well-differentiated carcinoma (n = 65). In agreement with the in vitro results, TGF-alpha expression was significantly increased in neoplastic thyrocytes, as compared to their normal counterpart. The results indicate that, as in the mammary and salivary glands, down-regulation of IL-6 expression may represent a marker of undifferentiated thyroid carcinoma.
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PMID:Reduced expression of interleukin 6 in undifferentiated thyroid carcinoma: in vitro and in vivo studies. 951 26

Tissue recombinants composed of adult human prostatic epithelium (hPrE) and rat urogenital sinus mesenchyme (rUGM) were grafted beneath the renal capsule of athymic rodent hosts. The pseudostratified human epithelium initially became multilayered, solid epithelial cords emerged, grew into the surrounding mesenchyme and canalized to regenerate a pseudostratified epithelium. Basal cells expressed cytokeratins 5 and 14, while luminal cells expressed cytokeratins 8 and 18, prostate specific antigen and prostatic acid phosphatase. The rat mesenchymal component differentiated into thick sheets of smooth muscle, characteristic of the human but not the rat prostate. These findings indicate that epithelial-mesenchymal interactions were reciprocal. Rat UGM induced adult hPrE to form new ductal-acinar tissue, involving epithelial proliferation, ductal branching morphogenesis and functional cytodifferentiation. Concurrently the epithelium dictated smooth muscle differentiation and patterning. Species-specific reverse transcriptase polymerase chain reaction SC (RT-PCR) analysis of the tissue recombinants was performed to separately examine the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), TGF-beta 1, and TGF-beta 3 in the epithelium, stroma and host components of the graft. All of these genes, except TGF-beta 1, were expressed in all three tissues. Human TGF-beta 1 was not detected, indicating that this gene was not expressed in human prostatic epithelium but was present in stroma.
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PMID:Interactions between adult human prostatic epithelium and rat urogenital sinus mesenchyme in a tissue recombination model. 969 7

The effects of transforming growth factor-alpha (TGF-alpha) on cell growth were studied in human glioma U251 cells transfected with antisense TGF-alpha vectors (pcDNAI.neo). Several antisense clones showed a marked decrease in growth rate in serum-free medium but not in medium containing 10% FBS, compared with those of parental cells and clones from sense or vector transfectants. Antisense clones also produced fewer and smaller colonies in anchorage-independent growth assays. Moreover, there was a reduction in TGF-alpha expression in these antisense clones at both the protein and mRNA levels, as determined by enzyme linked immuno-sorbent assay and reverse transcriptase polymerase chain reaction analysis. A U251 clone transfected by TGF-alpha antisense in a different vector (pMT/Ep) also showed a marked suppression in cell growth and TGF-alpha mRNA level. Finally, transfected clones with either vector system, showed decreased tumorigenicity in nude mice. In summary, a strong correlation between the inhibition of glioma cell growth and TGF-alpha expression was obtained from two different plasmid vectors, indicating that the expression of TGF-alpha could be specifically and effectively down-regulated by TGF-alpha antisense vector, which in turn led to growth inhibition. These studies suggests that TGF-alpha plays an essential role in controlling human glioma cell proliferation and may serve as a potential target for treatment of malignant glioma.
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PMID:Transforming growth factor-alpha antisense vectors can inhibit glioma cell growth. 1053 24

Placenta growth factor (PlGF) is a dimeric glycoprotein, structurally and functionally related to the vascular endothelial growth factor, a potent angiogenic/permeability factor known to play a role in the neoangiogenesis during wound repair. In this study we evaluated the expression of PlGF in human keratinocytes and investigated its possible role in wound healing. Northern blot analysis on cultured keratinocytes revealed a 1.7 kb mRNA transcript and reverse transcriptase-polymerase chain reaction allowed the detection of two PlGF isoforms generated by alternative RNA splicing. PlGF and vascular endothelial growth factor homodimers as well as vascular endothelial growth factor/PlGF heterodimers could be detected in keratinocyte conditioned medium. Increased expression of both PlGF mRNA and protein was observed upon treatment of keratinocytes with epidermal growth factor, transforming growth factor-alpha, transforming growth factor-beta, and interleukin-6, all cytokines present at the wound site during the early phase of repair. The analysis of human full-thickness healing wounds revealed appreciable levels of PlGF mRNA and protein in the migrating keratinocytes starting from day 3 after injury, and increasing at day 5. At day 7 PlGF mRNA was no longer detectable, while the protein was still expressed by migrating suprabasal keratinocytes. At day 13, when the wound had reepithelialized, PlGF immunostaining was completely negative. By in situ hybridization an intense signal for PlGF was also found on endothelial capillaries adjacent to the wound. These data demonstrate that keratinocytes are a source of PlGF during wound healing in vivo and indicate a role for this factor in the neoangiogenesis process associated with cutaneous wound repair.
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PMID:Placenta growth factor is induced in human keratinocytes during wound healing. 1095 Dec 73


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