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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about the mechanism(s) underlying hyperpigmentation in lentigo senilis. We have previously reported that keratinocyte-derived endothelins are intrinsic paracrine mitogens and melanogens for human melanocytes and that they play an essential role in stimulating ultraviolet-B-induced melanogenesis. In this study, we have used immunohistochemistry and reverse transcriptase polymerase chain reaction analysis to clarify the role of the endothelin cascade, including endothelin production, processing by endothelin-converting enzyme, and expression of the endothelin B receptor, in the hyperpigmentary mechanism(s) involved in lentigo senilis. The number of tyrosinase immunopositive melanocytes in lentigo senilis lesional skin was increased 2-fold over the perilesional epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated relatively stronger staining in the lesional epidermis than in the perilesional epidermis. Reverse transcriptase polymerase chain reaction analysis concomitantly demonstrated accentuated expression of transcripts for endothelin-1 and for the endothelin B receptor in lentigo senilis lesional skin, which was accompanied by a similar accentuated expression of tyrosinase mRNA compared with the perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor alpha, was consistently upregulated in the lentigo senilis lesional epidermis as determined at the transcriptional level and by immunostaining, whereas interleukin-1alpha was downregulated. In contrast, endothelin-converting enzyme 1alpha mRNA was not substantially increased in the lesional epidermis. These findings suggest that an accentuation of the epidermal endothelin cascade, especially with respect to expression of endothelin and the endothelin B receptor, plays an important role in the mechanism involved in the hyperpigmentation of lentigo senilis.
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PMID:The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis. 1128 25

The mechanisms of estrogen and progesterone in human cutaneous pigmentation are largely unknown. The molecular identification of estrogen receptor (ER) and progesterone receptor (PR) in the human melanocytes is of great importance to understand the mechanisms. We performed immunocytochemistry analysis and demonstrated that ER and PR were expressed in the cytoplasms and nuclei of human melanocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis confirmed the expression of ER and PR at the transcriptional level. Despite of the presence of ER and PR, the physiological and pregnant levels of estrogen and progesterone showed inconsistent effects on the proliferation and tyrosinase activity of cultured human melanocytes. These results suggest that human melanocytes express ER and PR, which have a donor-specific action in human pigmentation. Further studies are needed to elucidate the induction mechanism and functions of these receptors, and the role of estrogen and progesterone in melanocytes.
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PMID:Donor specific response of estrogen and progesterone on cultured human melanocytes. 1185 May 90

Cutaneous melanomas have been found to express several immunogenic differentiation melanoma-associated antigens (MAAs) that have been suggested to play an important role in disease outcome. Adaptive host immunity to MAAs has shown some level of control on melanoma progression. To date, there has been no definitive report correlating the level of differentiated MAAs gene expression in melanomas with overall disease outcome. Metastasis of melanoma to distant visceral organ sites usually indicates a survival of less than 1 year; however, a subset of patients who undergo cytoreductive surgery of distant metastases survive for a longer period. We hypothesized that the gene expression level of differentiation MAAs in metastatic melanoma (AJCC stage IV) lesions would be predictive of survival. We focused on three known differentiation MAAs: tyrosinase (TYR), TYR-related protein 2 (TRP-2), and melanoma antigen recognized by T cells 1 (MART-1); all three of them are known to induce immune responses in melanoma patients and are frequently expressed in melanomas. A quantitative reverse-transcriptase RealTime PCR (qRT) assay was developed for these MAAs to assess mRNA expression in metastatic melanoma tumors obtained from cytoreductive surgery of AJCC stage IV melanoma patients (n = 35). Patients were followed up for over 60 months. There was a variation in mRNA copy levels for individual MAAs in melanoma tumors. Elevated MAA mRNA copy levels of TYR and TRP-2 significantly (P < 0.03 and < 0.009, respectively) correlated with improved overall survival. Patients having at least one MAA expressed in their tumors had a significantly (P = 0.01) better overall survival (median 16 months). These studies demonstrate that levels of differentiated MAA mRNA expression of advanced-stage metastatic melanomas can be used as molecular predictive factors of disease outcome. The studies also imply that an assessment of melanoma tumor MAAs may provide a stratification factor targeted for active-specific immunotherapy.
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PMID:Expression of differentiation melanoma-associated antigen genes is associated with favorable disease outcome in advanced-stage melanomas. 1254

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.
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PMID:Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy. 1268 15

Laborious molecular genotyping and variegated gene expression are two widely encountered issues for transgenic mouse studies. To facilitate genotyping in the FVB/N albino background and to reduce variegated expression, we successfully generated double-tagged transgenic mice for direct visual genotyping with the coat color phenotype derived from tyrosinase cDNA driven by the tyrosinase promoter and with simultaneous high enhanced green fluorescent protein (EGFP) expression driven by the promoter of RNA polymerase II large subunit gene. Incorporation of insulator into a transgene construct achieved high efficiency of transgene expression in more than 90% of the founders. EGFP was detected as early as the one-cell fertilized egg and lasted for the whole embryo development, as well as in all of the adult tissues examined. The coat color-tagged green mice offer opportunities in applications such as tissue transplantation, lineage tracing, chimera biology, RNA interference, and other transgenic studies.
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PMID:Coat color-tagged green mouse with EGFP expressed from the RNA polymerase II promoter. 1517 Jun 98

The activity of melanosome-associated tyrosinase in human melanocytes differs based on racial skin type. In melanocytes from Black skin, tyrosinase activity is high while in White melanocytes the activity of the enzyme is low. Recent studies suggest that low tyrosinase activity in White melanocytes may be due to an acidic pH environment within the melanosome. Because sodium/hydrogen (Na(+)/H(+)) exchangers (NHEs) are known to regulate intracellular pH, melanocytes were treated with NHE inhibitors to determine what effect this inhibition might have on tyrosinase activity. Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity. This inhibition was not due to either direct enzyme inhibition or to a decrease in tyrosinase abundance. In contrast, treatment of White melanocytes with EIPA, cimetidine, or clonidine resulted in little inhibition of tyrosinase activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis showed that both Black and White melanocytes expressed mRNA and protein for NHE-1, NHE-3, NHE-5, NHE-6, and NHE-7. Immunohistochemical analysis showed that NHE-7 and NHE-3 co-localized with the melanosomal protein, Tyrosinase Related Protein-1 (TRP-1). In addition, the vesicular proton pump, vesicular ATPase (V-ATPase), was found to be present in both White and Black melanosomes, indicating that organelles from both racial skin types are capable of being acidified. The results suggest that one or more NHEs may help regulate melanosome pH and tyrosinase activity in human melanocytes.
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PMID:The relationship between Na(+)/H(+) exchanger expression and tyrosinase activity in human melanocytes. 1526 99

Skin and hair colour mostly depend on the activity of melanogenic melanocytes. Numerous proteins involved in melanocyte function have been identified including pMel-17, Mitf-M, Sox10, tyrosinase, tyrosinase related proteins-1 (TRP-1) and -2 (TRP-2). In the hair, melanogenic activity occurs only during the anagen phase of the hair cycle. In order to evaluate the implications of some known melanogenic proteins in human hair pigmentation, we performed immunohistochemical studies to reveal the expression of pMel-17, Mitf-M, tyrosinase, TRP-1 and TRP-2 in active bulb melanocytes of eumelanic brown and black anagen hairs of different ethnic origins, e.g. brown Caucasian, black Asian and African hairs. The labelling was compared with that observed in Caucasian and African scalp epidermis (interfollicular epidermis) melanocytes. We found that while pMel-17, TRP-1 and TRP-2 were expressed in epidermal melanocytes irrespective of ethnic origin and melanin content of the scalp epidermis, Mitf-M and tyrosinase expression were clearly evidenced only in pigmented epidermis, e.g. African scalps. Regarding human hair, pMel-17, Mitf-M, tyrosinase and TRP-1 were detected in a similar manner in active bulb melanocytes of brown and black hairs. In contrast and unexpectedly, TRP-2 could not be detected in hair bulb melanocytes, whatever the hair colour and ethnic origin. The lack of TRP-2 was further confirmed by western blot analyses. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on hair bulb mRNA demonstrated that Mitf-M, tyrosinase and TRP-1 amplimer signals were easily detected, whereas the TRP-2 amplimer signal was barely detectable. Furthermore Sox10 was not detected in hair bulb. Altogether our results suggest that the absence of detectable level of TRP-2 is due to transcriptional control in active melanocytes of human eumelanic hair bulbs. According to the absence of TRP-2 in melanin-producing melanocytes of brown and black hair bulbs, one must consider that eumelanogenesis as well as brown and black colour do not require TRP-2 expression in human hair.
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PMID:Absence of TRP-2 in melanogenic melanocytes of human hair. 1535 35

Prophenoloxidase (proPO) is a melanin-synthesising enzyme that plays important roles in immune responses by crustaceans. Previously, we cloned and characterized proPO-I from white shrimp, Litopenaeus vannamei. In the present study, a novel prophenoloxidase-II (proPO-II) cDNA was also cloned from haemocytes of L. vannamei using oligonucleotide primers and reverse-transcriptase polymerase chain reaction (RT-PCR). Both 3'- and 5'-regions were isolated by the rapid amplification of complementary (c)DNA end (RACE) method. The 2504-bp cDNA contained an open reading frame (ORF) of 2073 bp, an 84-bp 5'-untranslated region, and a 347-bp 3'-untranslated region containing the poly A tail. The molecular mass of the deduced amino acid sequence (691 amino acids) was 78.8 kDa with an estimated pI of 6.07. It contains two putative tyrosinase copper-binding motifs and a conserved C-terminal region common to all known proPOs. Comparisons of the amino acid sequences showed that white shrimp proPO-II is more closely related to the proPO of other penaeids than to that of crayfish, lobsters, crab, or a freshwater prawn, and is the ancestor type of known penaeid proPOs. proPO-I and proPO-II messenger (m)RNAs of shrimp were located on different loci, and were constitutively expressed mainly in haemocytes. The transcriptional regulation of these two proPOs in shrimp at different molt stages, those administered dietary sodium alginate, and those challenged with Vibrio alginolyticus were surveyed. The results showed that the proPOs may be directly involved in the acute-phase immune defence, and proPO-II may contribute earlier to immune defence in shrimp injected with V. alginolyticus, and it may be regulated by ecdysone. However, a similar effect was found by stimulating proPO-I and proPO-II mRNA expression in shrimp fed a sodium alginate-containing diet. Results of this study provide a basis for developing a comprehensive understanding of expression/function relationships of individual proPOs in shrimp.
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PMID:A second proPO present in white shrimp Litopenaeus vannamei and expression of the proPOs during a Vibrio alginolyticus injection, molt stage, and oral sodium alginate ingestion. 1898 57

Sentinel lymph node (SLN) biopsy has become integral in the staging of patients with melanoma, and entails detailed histologic examination with immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase transcripts has been used to increase sensitivity but requires a dedicated piece of tissue that does not undergo histologic examination. We developed a nested RT-PCR assay for tyrosinase applicable on paraffin-embedded tissue and applied this to a series of SLNs from pediatric patients with melanoma. Thirty-six SLNs from 4 females and 4 males were included in the study. Eight lymph nodes with reactive changes were included as controls. SLNs were examined histologically and immunohistochemically for S100, tyrosinase, and MART1. Seven patients had between 1 and 4 morphologically-positive SLNs and one patient had negative SLNs (HISTO+; 12/36, 33%). Three lymph nodes were excluded from molecular analysis owing to inadequate RNA, and 29 of the remaining 33 nodes were positive (MOL+; 88%). All patients had at least 1 SLN positive by RT-PCR. Twelve were HISTO+/MOL+; 17 were HISTO-/MOL+; and 4 were HISTO-/MOL-. All control lymph nodes were negative for tyrosinase transcripts. The application of RT-PCR for tyrosinase to paraffin-embedded tissue significantly increased the number of positive SLNs and upstaged one patient from negative to positive. The prognostic implications of such findings require further investigation, especially in the pediatric age group. Nonetheless, this technique provides a useful tool to determine the clinical significance of RT-PCR positivity in melanoma SLNs.
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PMID:Increased detection of metastatic melanoma in pediatric sentinel lymph node biopsies using RT-PCR on paraffin-embedded tissue. 2057 43


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