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 epidermal growth factor (EGF) system is a rapidly expanding system of growth factors involved in many aspects of normal and cancerous growth. We have developed a method for the quantitation of mRNA coding for all six growth factors activating the human EGF receptor (HER-1) and for the quantitation of mRNA for the receptors HER-1 and its preferred dimerization partner, HER-2. The method is based on the generation of specific RNA standards, which are amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) with the sample RNA and a set of calibrators. The resulting calibration curve is used to quantitate the unknown samples, which require only a single RT-PCR reaction. Our method has the advantage that quantitation is based on coamplification of an internal RNA standard, thereby controlling both the PCR and RT reactions. In addition, the RNA standards for all growth factors and receptors are combined in a single RT reaction, which minimizes variation and allows the quantitation of all eight mRNA species with only 0.1 microg RNA. This makes the method suitable for studies in which the supply of material is limited. The developed method has enabled us to demonstrate that prostate stromal cells in primary culture express EGF, heparin-binding EGF (HB-EGF), amphiregulin, betacellulin, and epiregulin as well as the HER-1 and HER-2 receptors, whereas no transforming growth factor-alpha mRNA is found. Furthermore, activation of the EGF system in these cells by stimulation with HB-EGF or EGF in mitogenic doses causes a selective increase in the expression of amphiregulin and HB-EGF mRNA (more than 15-fold and 25-fold, respectively), whereas there is no increase in the expression of mRNA for the other growth factors or receptors. In accord with the increase in amphiregulin mRNA, the amount of amphiregulin peptide released from the cells is also increased. The selective induction of amphiregulin and HB-EGF by growth factor stimulation may represent a mechanism to amplify the initial growth factor signal in prostate stromal cells.
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PMID:Quantitation of the mRNA expression of the epidermal growth factor system: selective induction of heparin-binding epidermal growth factor-like growth factor and amphiregulin expression by growth factor stimulation of prostate stromal cells. 1098 99

The bronchial epithelium is a potential source of growth factors that could mediate airway fibrosis during the progression of diseases such as asthma and chronic bronchitis. We report that conditioned medium (CM) from normal human bronchial epithelial cells (NHBECs) contains mitogenic activity for human lung fibroblasts that is blocked by the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitor AG1478 and by neutralizing antibodies raised against heparin-binding epidermal growth factor-like growth factor (HB-EGF). Neutralizing antibodies against other EGF-R ligands (EGF and transforming growth factor-alpha) or other antibodies against growth factors (platelet-derived growth factors, insulin-like growth factor-1) had no affect on the mitogenic activity of NHBEC-CM. HB-EGF messenger RNA (mRNA) expression in NHBEC was detected by reverse transcriptase/polymerase chain reaction and Northern blot analysis. HB-EGF protein was detected by enzyme-linked immunosorbent assay. Vanadium pentoxide (V2O5), a fibrogenic metal associated with occupational asthma, caused a several-fold increase in HB-EGF mRNA expression and protein, whereas the inert metal titanium dioxide had no effect on HB-EGF expression. V2O5-induced HB-EGF mRNA expression was inhibited by the EGF-R tyrosine kinase inhibitor AG1478, the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and the MAP kinase kinase inhibitor PD98059. Finally, HB-EGF induced the production of fibroblast growth factor (FGF)-2 by human lung fibroblasts and anti-FGF-2 antibody partially blocked the mitogenic activity of NHBEC-CM on fibroblasts. These data suggest that HB-EGF is a fibroblast mitogen produced by NHBECs and that induction of an FGF-2 autocrine loop in fibroblasts by HB-EGF accounts for part of this mitogenic activity.
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PMID:Vanadium stimulates human bronchial epithelial cells to produce heparin-binding epidermal growth factor-like growth factor: a mitogen for lung fibroblasts. 1115 45

We studied expressions of various growth factors, their receptors, cell adhesion molecules and extracellular matrix components in Warthin's tumor of the salivary gland with immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Various growth factors and their receptors, such as transforming growth factor-alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HB-EGF), TGF-beta2, TG-beta3, insulin-like growth factor (IGF)-I and -II, vascular endothelial growth factor (VEGF), EGF receptor (EGFR), erb-B4, TGF-betaRI and II, Flt and Flk-1 and IGF receptor Ibeta, were found in epithelial cells and/or in some lymphoid cells. Fibronectin, laminin, collagen type IV and tenascin were found in stroma of the lymphoid tissue. Integrins such as alpha3beta1 and beta3, Thy-1, CD44 and VCAM-1 were also expressed in epithelial and/or lymphoid cells. These various proteins may interact and regulate the proliferation and cell attachment of both epithelial and lymphoid components in this unique tumor.
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PMID:Growth factors, extracellular matrix components and cell adhesion molecules Warthin's tumor. 1133 65

Accumulated evidence suggests that growth factors of the epidermal growth factor (EGF) family play an important role in the murine implantation process. In the sheep, however, the uterine distribution of these factors and their receptor, EGF receptor (EGF-R), during implantation is not known. This study examined the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), the potent EGF-family member, and EGF-R in the ovine uterus during the early implantation period. By reverse transcriptase-polymerase chain reaction and sequencing of the products, the presence of TGF-alpha and EGF-R mRNA transcripts were detected in the endometrium on Days 14, 16 and 20 (Day 0 = day of mating). Immunohistochemical analysis revealed that the luminal and glandular epithelial cells and some stromal cells of the endometrium and the trophectoderm were positive for TGF-alpha and EGF-R on Days 14 and 15. Distinct staining for TGF-alpha was observed in the glandular epithelium of deep endometrial areas and strong immunoreactivity for EGF-R was found in the trophectoderm. On Days 16, 18 and 20, although the staining pattern for TGF-alpha was similar to that on the previous days, the immunoreactivity for EGF-R in the stromal cells increased and that in the gland decreased. A distinct immunoreactivity for EGF-R was found in the trophectoderm throughout the days examined. These results suggest that TGF-alpha expressed in the endometrium and trophectoderm may exert effects locally on these tissues during implantation in sheep. Furthermore, it is speculated that the temporal changes in the uterine EGF-R distribution may be related to the endometrial microvascular development.
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PMID:Detection of transforming growth factor-alpha and epidermal growth factor receptor mRNA and immunohistochemical localization of their proteins in the ovine uterus during the early implantation period. 1281 85

Uterine expression of the epidermal growth factor (EGF) family of growth factors has not been studied in the dog. The present study looks at the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), which is the potent EGF family member, and for EGF receptor (EGF-R) in the canine uterus during the estrous cycle. The reverse transcriptase-polymerase chain reaction together with sequencing of the products confirmed the presence of their mRNA transcripts in the endometrium throughout the estrous cycle. Immunohistochemical analysis found clear positive staining for TGF-alpha and EGF-R in the luminal and glandular epithelia at proestrus and estrus. Immunoreactivity decreased at the early stage of diestrus. In the mid stage of diestrus, clear staining for TGF-alpha was again found in the glands of the luminal region, and staining for EGF-R was observed in all glands. Very little staining was seen at anestrus for either TGF-alpha or EGF-R. These results suggest that TGF-alpha expressed in the uterus may be involved in regulating growth, differentiation and regression in the endometrial epithelial cells during the estrous cycle in the dog.
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PMID:Detection of transforming growth factor-alpha and epidermal growth factor receptor mRNA and immunohistochemical localization of the corresponding proteins in the canine uterus during the estrous cycle. 1594 31

The majority of ovarian cancer patients are treated with platinum-based chemotherapy, but the emergence of resistance to such chemotherapy severely limits its overall effectiveness. We have shown that development of resistance to this treatment can modify cell signaling responses in a model system wherein cisplatin treatment has altered cell responsiveness to ligands of the erbB receptor family. A cisplatin-resistant ovarian carcinoma cell line PE01CDDP was derived from the parent PE01 line by exposure to increasing concentrations of cisplatin, eventually obtaining a 20-fold level of resistance. Whereas PE01 cells were growth stimulated by the erbB receptor-activating ligands, such as transforming growth factor-alpha (TGFalpha), NRG1alpha, and NRG1beta, the PE01CDDP line was growth inhibited by TGFalpha and NRG1beta but unaffected by NRG1alpha. TGFalpha increased apoptosis in PE01CDDP cells but decreased apoptosis in PE01 cells. Differences in extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling were also found, which may be implicated in the altered cell response to ligands. Microarray analysis revealed 51 genes whose mRNA increased by at least 2-fold in PE01CDDP cells relative to PE01 (including FRA1, ETV4, MCM2, AXL, MT3, TRAP1, and FANCG), whereas 36 genes (including IGFBP3, TRAM1, and KRT4 and KRT19) decreased by a similar amount. Differential display reverse transcriptase-PCR identified altered mRNA expression for TCP1, SLP1, proliferating cell nuclear antigen, and ZXDA. Small interfering RNA inhibition of FRA1, TCP1, and MCM2 expression was associated with reduced growth and FRA1 inhibition with enhanced cisplatin sensitivity. Altered expression of these genes by cytotoxic exposure may provide survival advantages to cells including deregulation of signaling pathways, which may be critical in the development of drug resistance.
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PMID:Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. 1606 61

In this study, we examined ErbB1 signaling in human basal and squamous cell carcinomas (BCC and SCC) of the skin in vivo. We used enzyme-linked immunosorbent assay, laser capture microdissection-coupled real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry to assess expression and activation levels of ErbB1 protein, ligands, and potential downstream effectors, in BCC and SCC tumors, stroma, and adjacent epidermis. Although total ErbB1 protein and mRNA were similar in cancerous and normal skin, we found that ErbB1 activation (phospho-Tyr(1068)) was greater in bulk SCC versus BCC or normal skin. In addition, three ErbB1 ligand transcripts (amphiregulin, heparin-binding epidermal growth factor-like growth factor, and transforming growth factor-alpha) were up-regulated in tumor cells of SCC but not BCC. Expression of these ligands was also increased in asymptomatic epidermis adjacent to both SCC and BCC, relative to normal skin. Interestingly, betacellulin transcript levels were inversely regulated compared with the other ligands. Consistently, downstream ErbB1 effectors (Erk1/2 and Akt) were activated in tumor cells of SCC but not of BCC and in adjacent epidermis of both BCC and SCC. These results demonstrate that ErbB1 signaling is hyperactive in tumor cells of SCC but not of BCC and in nearby asymptomatic epidermis of both tumor types. Our results suggest that targeting ErbB1 signaling might be of benefit in the treatment of SCC.
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PMID:Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin. 1752 75


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