Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma inhibitory activity (MIA) is a small soluble protein secreted by malignant melanoma cells and chondrocytes. Prior studies suggested that MIA expression was relatively tissue-specific, making it a potentially useful marker for melanoma. The current investigations sought to more clearly define the range of tumor/tissue-types where MIA is expressed, compared with expression of 4 other potential melanoma marker genes (tyrosinase melanoma antigen recognized by T cells [MART-1/MelanA], gp100, and melanoma growth-stimulatory activity [MGSA/Gro alpha]). Expression of these genes was assayed by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry in 23 melanoma tumor specimens and in 25 additional nonmelanoma or nonmalignant specimens. MIA, tyrosinase, and MGSA were expressed in most melanoma specimens. Specificity was highest for MART-1, followed by MIA and tyrosinase. Increasing the number of cycles of amplification from 35 to 40 increased sensitivity but decreased specificity of most markers, though MIA was relatively robust. MIA mRNA was also detected in carcinomas of the colon, ovary, kidney, and head/neck, as well as in normal laryngeal epithelium. Although MIA discriminated melanoma from nonmelanoma at least as well as tyrosinase, no single mRNA marker had accuracy greater than 71%, raising potential concern about application of these particular mRNA markers to the minimal disease setting. HUM PATHOL 31:1381-1388.
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PMID:Expression of melanoma inhibitory activity in melanoma and nonmelanoma tissue specimens. 1111 13

The molecular and genetic events that contribute to the genesis and progression of cutaneous malignant melanoma are poorly understood, attributable in large part to the different genetic alterations accompanying tumorigenesis. Inhibitor of kinase 4a (INK4a) is often inactivated in families with hereditary melanoma. Loss of INK4a/alternate reading frame (ARF) in mice is associated with increased incidence of other tumors such as lymphoma and fibrosarcoma. However, the incidence of melanoma in INK4a/ARF-deficient mice is very low. Our previous studies have revealed that the CXC chemokine, CXCL1, is overexpressed in human malignant melanoma cells and is linked to transformation of immortalized murine melanocytes. To study the direct role of CXCL1 on the genesis of primary melanoma lesions, transgenic mouse lines were established that express the murine homologue of CXCL1, murine macrophage inflammatory protein 2 (MIP-2), under the transcriptional control of the tyrosinase promoter/enhancer (Tyr-MIP-2) in the mice that were deficient or not deficient for INK4a/ARF. Strong MIP-2 immunoreactivity was associated with pigmented melanocytes in the hyperproliferative hair follicles in the Tyr-MIP-2 transgenic mice, and the level of MIP-2 expression was similar in both INK4a/ARF heterozygous or wild-type mice. After treatment of mice with 7,12-dimethylbenz(a)anthracene, cutaneous melanomas formed in 12% (17/145) of the Tyr-MIP-2 transgene-positive mice, whereas only 2% (3/146) of the Tyr-MIP-2 transgene-negative mice developed melanoma. When melanocytes cultured from MIP-2 transgenic mice null for INK4a/ARF were transplanted into nude mice, melanoma formation occurred in 83% (10/12) of the cases with a latency period of 3 months. However, no melanoma lesions arose in nude mice injected with INK4a/ARF -/- melanocytes, which did not express the MIP-2 transgene. Our results demonstrate that constitutive expression of MIP-2 in INK4a/ARF-deficient melanocytes facilitates formation of malignant melanoma.
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PMID:Induction of melanoma in murine macrophage inflammatory protein 2 transgenic mice heterozygous for inhibitor of kinase/alternate reading frame. 1171 44