Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cutaneous melanocytic neoplasms are known to acquire variable characteristics of neural crest differentiation. Melanocytic nevus cells in the dermis and desmoplastic melanomas often display characteristics of nerve sheath differentiation. The extent and nature of neuronal differentiation characteristics displayed by primary and metastatic melanoma cells are not well understood. Here, we describe induction of a juvenile isoform of microtubule-associated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the differentiation inducer hexamethylene bisacetamide. Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendritic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp75), a melanocyte differentiation marker. In a panel of cell lines that represent melanoma tumor progression, MAP-2c mRNA and the corresponding approximately 70-kd protein could be detected predominantly in primary melanomas. Immunohistochemical analysis of 61 benign and malignant melanocytic lesions showed abundant expression of MAP-2 protein in melanocytic nevi and in the in situ and invasive components of primary melanoma, but only focal heterogeneous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1-negative. This reciprocal staining pattern in vivo is similar to the in vitro observation that induction of the neuronal marker MAP-2 in metastatic melanoma cells is accompanied by selective extinction of the melanocytic marker TYRP1. Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and malignant melanocytes in the dermis can express markers of neuronal differentiation.
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PMID:Expression of microtubule-associated protein 2 in benign and malignant melanocytes: implications for differentiation and progression of cutaneous melanoma. 1139 88

Objective To observe the molecular mechanism of Bushen Quban Granule (BQG) for inhibiting the synthesis of intracellular melanin. Methods Twenty SPF grade female SD rats were di- vided into four groups by completely randomized method, i.e., the control group (fed with normal saline) , high, middle, and low dose BQG groups (administered with BQG at 4. 8, 2. 4, 1. 2 g/kg by gastrogavage, equivalent to 24, 12, and 6 times clinical doses, respectively, twice per day for 3 days in total) , 5 in each group. Drug containing serum was collected. Expressions of melanocortin 1 receptor (MC1 R) , mi- crophthalmia-associated transcription factor ( MITF) , tyrosinase ( TYP) , tyrosinase-related protein I (TYRP1) , and tyrosinase-related protein 2 (TYRP2) at the mRNA level were detected by RT-PCR. Ex- pressions of phosphorylated-extracellular regulated MAP kinasel/2 (p-ERK) , TYP, TYRP1 and TYRP2 at the protein level were detected by Western blot. Intracellular melanin contents were determined by NaOH dissolving method. Activities of tyrosinase were determined by Dopa pigment method, and the cell viability was detected by MTT. Results Compared with the control group, expressions of MC1R, MITF, TYP, TYRP1 and TYRP2 at the mRNA level were down-regulated (P <0. 05), and those of TYP, TYRP1 and TYRP2 at the protein level were also down-regulated (P <0. 05), intracellular contents of melanin and the activity of tyrosinase decreased (P <0. 05) , but the level of p-ERK and the proliferation of cells increased in each medicated group (P <0. 05). When ERK was inhibited by its inhibitor PD98059, there was no sta- tistical difference in expressions of MC1 R or MITF at the mRNA level among all medicated groups (P > 0. 05). Compared with the control group, mRNA expressions of TYP, TYRP1 and TYRP2 decreased in the high dose BQG group (P <0. 05), but with no significant difference in protein expressions of p-ERK, TYP, TYRP1 and TYRP2 (P >0. 05). There was no statistical difference in the content of melanin, the activity of TYP, or the proliferation of cells between the control group and the high dose BQG group (P >0. 05). Con- clusion BQG could inhibit the synthesis of intracellular melanin through up-regulating p-ERK to inhibit the expression of tyrosinase and its related proteins.
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PMID:[Mechanisms Involved in the Inhibition of Melanin Synthesis by Bushen Quban Granule]. 3064 34