Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 antiproliferative effects of somatostatin and its analogs on human pancreatic cancers were studied: (1) by evaluating the gene expression of somatostatin receptor (sstr) subtypes in human pancreatic cancer cell lines and cancer tissue specimens, (2) by evaluating the antiproliferative effects of somatostatin analogs, and (3) by evaluating the effect of sstr-2 cDNA transduction. Using a reverse transcriptase polymerase chain reaction (RT-PCR), the gene expression of five sstr subtypes (sstr-1 to -5) was examined in eight cell lines, and in ten pancreatic cancer tissues and in the normal surrounding pancreatic tissues. The antiproliferative effects of somatostatin (SS) -14 and its two analogs (SMS 201-995, RC-160) were examined by means of an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue)) assay on three cell lines and Panc-1 transfectants with human sstr (hsstr)-2A cDNA. Sstr-2 was expressed in all samples tested. All examined cell lines simultaneously expressed sstr-2 and -5, while most of the examined pancreatic cancer tissues did not express both of these subtypes simultaneously. Somatostatin analogs inhibited epidermal growth factor (EGF)-stimulated pancreatic cancer cell proliferation. The cell proliferation was further and significantly inhibited by 14% in stable transfectants of Panc-1 cells with hsstr-2A. Based on these findings, it is concluded that somatostatin analogs with their antiproliferative effects mediated by sstr-2 could be potentially useful in the treatment of pancreatic cancers.
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PMID:Expression of somatostatin receptor subtypes and growth inhibition in human exocrine pancreatic cancers. 1118 Aug 77

Malignant melanoma is a neuroendocrine tumor that contains somatostatin receptors (SSTRs). Adjuvant therapy for melanoma is limited. Because melanomas arise from neural crest cells, we sought to evaluate the distribution of SSTR subtypes found in these tumors and their functional significance by imaging with 111In-pentetreotide scintigraphy (OctreoScan). Octreotide binds with greatest affinity to SSTR2 and SSTR5. Studying the expression of SSTRs in melanoma may demonstrate a potential role for octreotide in the treatment of melanoma. A series of 23 melanomas from 17 patients who underwent resection of regional or distant metastases were evaluated for the presence of SSTRs by the reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for SSTR1 through SSTR5. Identity of RT-PCR products was confirmed by Southern blot analysis. Sixteen patients underwent preoperative OctreoScan. SSTR1 was expressed in 96% of tumors, SSTR2 in 83%, SSTR3 in 61%, SSTR4 in 57%, and SSTR5 in 9%. OctreoScan imaged 63% of tumors. There was no correlation between SSTR subtype expression and OctreoScan result. Most of the melanomas expressed mRNA for SSTR1 and SSTR2, with approximately half expressing SSTR3 and SSTR4. The SSTR mRNA for SSTR2 appears to be transcribed into functional protein that binds 111In-pentetreotide in more than half of these patients. Although OctreoScan has limited sensitivity for localizing melanomas, tumors that can be imaged by OctreoScan may be amenable to adjuvant therapy with octreotide or targeted therapy with high-energy radioisotope-labeled octreotide. These studies clearly define melanoma as a neuroendocrine tumor, which may open new avenues for tumor control.
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PMID:Distribution and functional significance of somatostatin receptors in malignant melanoma. 1134 89

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.
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PMID:Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component. 1147 72

Acid secretion first appears in the stomach during the later stages of fetal development. Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine, acetylcholine and the inhibitory actions of somatostatin on their respective receptors. A semi-quantitative reverse transcriptase-polymerase chain reaction method for the determination of changes in mRNA expression for these receptors was developed and correlated with known changes in gastric acidity. Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) was used as a reference and an internal standard. The antrum and fundus from four age groups were assayed: 80 days of gestation, 110 days of gestation, term (145 days) and adult animals. The CCK B/gastrin and the histamine (H(2)) receptor mRNA were significantly lower in samples from the fundus of fetuses, from 80 and 110 days of gestation when compared with the adult fundus. Histamine receptor mRNA in the antrum was also significantly lower in the 80 and 110 days of gestation samples relative to the term fetal antrum. Somatostatin II receptor mRNA levels in the antrum decreased with increasing age with no change in the fundus. These findings suggest that changes in receptor gene expression, may be responsible for the diminished gastric acidity and responsiveness observed in the fetal stomach.
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PMID:Expression of receptors regulating gastric acidity in the developing sheep stomach. 1149 84

The increasingly popular use of somatostatin analogs in clinical practice for both diagnostic and therapeutic purposes prompted extensive investigations on somatostatin receptor (sst) expression in human tumors by autoradiography, nucleic acid analysis and, recently, immunohistochemistry (IHC). The currently employed radiotracer for scintigraphy (Octreoscan) is octreotide, a somatostatin analog having a high affinity for sst types 2, 3, and 5. In this study on 25 patients, we compared sst 2, 3, and 5 expression in surgical and biopsy specimens of lung tumors, as revealed by immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR), with the octreoscan outcome (which was positive in 20/25 cases). By IHC, the tumors mainly expressed sst2 (17/25, 68%) at the cell membrane level, while sst 3 and 5 were detected in a fraction of cases (24% and 20%, respectively). Comparing RT-PCR and IHC data, a correlation was found in 83.3% of cases, while octreoscan findings and sst expression were correlated in 22/25 cases (88%). In addition, cytological and biopsy specimens expressed the same sst type found in the corresponding surgical sample, thus indicating that a cell membrane sst immunoreactivity in a biopsy reliably predicts the tumor-receptor profile before its resection. Finally, sst expression was not restricted to neuroendocrine lung tumors, but was also a feature of some non-neuroendocrine carcinomas, although to a lesser extent. The occasional expression of sst subtypes in intratumoral lymphocytes, endothelia and necrotic areas is an additional feature to be considered in the interpretation of Octreoscan findings, since the in vivo procedure does not allow to define the sst cellular distribution. IHC can therefore be usefully coupled to radionuclear investigations to better characterize the sst cellular location and subtype in lung tumors.
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PMID:Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. 1178 52

The chemotherapeutic drug doxorubicin and the anti-proliferative long-acting somatostatin analogue octreotide, both used in cancer treatment, have been shown to increase the expression of the p53 tumour suppressor protein. In the present study, we demonstrate by Western-blot analysis that, in addition to the p53 protein, these molecules were able to induce the expression of a shorter protein with an apparent molecular mass of 40 kDa (p40), recognized by antibodies raised against the N-terminus of p53. This induction was present in tumoral and non-tumoral cells and did not depend on the status of the endogenous p53 protein. The p40 protein was significantly induced after 3 h of cell treatment with doxorubicin or octreotide, remained stable until 24 h and was located in the nuclear extract. Using reverse primers corresponding to each exon of the p53 gene, only one transcript was amplified by reverse transcriptase-PCR. This suggested that p40 was issued from a post-translational modification and not from an alternative splicing. This protein was not recognized by the PAb421 antibody, suggesting that it was issued from a cleavage of the p53 C-terminal region (p40deltaC). Furthermore, this cleavage was not dependent on caspase activity. In conclusion, these results support the hypothesis that this post-translational modification plays a significant role in the regulation of multiple p53 signalling pathways. These results also suggest that octreotide, a molecule with different signalling pathways, was able as doxorubicin to generate a p53 breakdown product.
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PMID:Doxorubicin and octreotide induce a 40 kDa breakdown product of p53 in human hepatoma and tumoral colon cell lines. 1204 55

By combining a Drosophila genome data base search and reverse transcriptase-PCR-based cDNA isolation, two G-protein-coupled receptors were cloned, which are the closest known invertebrate homologs of the mammalian opioid/somatostatin receptors. However, when functionally expressed in Xenopus oocytes by injection of Drosophila orphan receptor RNAs together with a coexpressed potassium channel, neither receptor was activated by known mammalian agonists. By applying a reverse pharmacological approach, the physiological ligands were isolated from peptide extracts from adult flies and larvae. Edman sequencing and mass spectrometry of the purified ligands revealed two decapentapeptides, which differ only by an N-terminal pyroglutamate/glutamine. The peptides align to a hormone precursor sequence of the Drosophila genome data base and are almost identical to allatostatin C from Manduca sexta. Both receptors were activated by the synthetic peptides irrespective of the N-terminal modification. Site-directed mutagenesis of a residue in transmembrane region 3 and the loop between transmembrane regions 6 and 7 affect ligand binding, as previously described for somatostatin receptors. The two receptor genes each containing three exons and transcribed in opposite directions are separated by 80 kb with no other genes predicted between. Localization of receptor transcripts identifies a role of the new transmitter system in visual information processing as well as endocrine regulation.
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PMID:Functional annotation of two orphan G-protein-coupled receptors, Drostar1 and -2, from Drosophila melanogaster and their ligands by reverse pharmacology. 1216 55

The production and release of GH has been demonstrated in a variety of extra-pituitary tissues. In this respect insulin-producing pancreatic tumours are also of interest because it has been observed that GH may promote islet cell proliferation. However, these effects have only been related to GH of pituitary origin and the possibility of local production of GH with autocrine-/paracrine effects has not been considered. In this study, a reverse transcriptase polymerase chain reaction (RT-PCR) was used to demonstrate the presence of GH mRNA in pancreatic tissue of five healthy dogs and insulinomas of 14 dogs. After Southern blotting of the RT-PCR products, blots were hybridized using a canine-specific GH-probe and quantified using phosphor imaging. GH gene expression was further demonstrated by in situ hybridization using a canine digoxigenin-labelled GH-specific cDNA probe. In addition, GH immunohistochemistry was performed. In five samples of normal pancreatic tissue a weak hybridization signal was found. This signal was significantly higher in nine of 12 primary tumours. In ten of 11 metastases there was a positive hybridization signal, and this signal was also significantly higher than in the primary tumours. In situ hybridization in one sample demonstrated that GH mRNA was only produced in the tumour cells. The local production of GH was confirmed by positive staining of tumour tissue with anti-GH antibodies in ten of 12 samples. It is concluded that canine insulinomas express the gene encoding GH mRNA. The locally produced GH may have an autocrine/paracrine effect on tumour progression. The relatively high expression levels in metastases of these tumours may be related to the low inhibitory influence of somatostatin outside the pancreas.
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PMID:Locally produced growth hormone in canine insulinomas. 1243 12

Somatostatin (SST) plays an important regulatory role in the physiological control of various organs including the prostate. Somatostatin receptors (SSTRs) and SST analogs are potential targets for prostate cancer treatment, especially since it has been shown that SST analogues are clinically effective in the treatment of advanced prostate cancer. The presence of SST containing neuroendocrine (NE) cells in the epithelium of the human prostate and their suggested role in the paracrine regulation of this gland prompted us to study the potential expression of somatostatin receptors (SSTRs) in human prostatic tissue and prostate cancer cell lines. Using the reverse transcriptase polymerase chain reaction (RT-PCR), we found the SSTR subtypes 1-3 in stromal cells and in prostate cancer cell lines LNCaP, PC-3 and DU 145. Immunohistochemical analysis of 27 radical prostatectomy specimens demonstrated the presence of hSSTR1 in a subpopulation of cancerous and NE cells, whereas hSSTR2 was found in the stroma, peritumoral blood vessels and tumor cells. Receptor subtype 3 was demonstrated to be present on the cell membrane of BPH and malignant areas. A strong immunoreaction (IR) of hSSTR4 was found in tumor cells, as compared with a less intense IR in adjacent BPH areas. Somatostatin receptor subtype 5 was not detectable. Western blot analysis revealed immunoreactive bands of molecular weight between 44-60 kDa. In summary, the present study clearly demonstrates the presence of hSSTR1-3 in tumoral and nontumoral epithelial cells as well as in the stromal compartment, whereas hSSTR4 was found to be confined to epithelial cells, and SSTR5 was not detectable.
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PMID:Localization and mRNA expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines. 1247 41

Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1-sst5). Pineal parenchymal tumor (PPT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtpe sst2, evidenced an about sixfold higher level in in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.
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PMID:Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors. 1270 86


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