Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy.
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PMID:The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance. 1726 41

Malignant melanoma remains the most life-threatening skin cancer to date. What makes it worse is the incidence keeps increasing worldwide, including in China. Notably, clinical studies revealed the distinct features in the Chinese population differing from those in Caucasians, which give hints to variant mechanisms underlying. Therefore, it is of great importance to generate a cell line with similar background for melanoma research in Chinese even Asian patients. However, most melanoma cell lines in use are derived from Caucasians, thus, we established one novel metastatic melanoma cell line, FLFMM-34, derived from a Han Chinese woman. The cell line showed positive for S100, HMB45, vimentin and melan-A. Chromosome analysis revealed multiple structural aberrations. Gene-mutation analysis identified that FLFMM-34 cells had BRAF(V600E) mutation and deletions of exon 2 and 3 in p16/CDKN2A. Importantly, two novel mutations including TP53(P33R) and TP53(R142H) have been detected. RT-PCR results showed that FLFMM-34 cells expressed a higher mRNA level of cyclinD1 than three other melanoma cell lines, WM793B, 1205Lu and A2058. In addition, in vivo mice model demonstrated that the cells could be transplanted into the subcutis of nude mice and produced tumors associated with lymphoid node metastases. In conclusion, these data indicate that FLFMM-34 cell line can be employed as a suitable model for melanoma research in Chinese Han population.
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PMID:Establishment of a novel Chinese metastatic melanoma cell line showing the new cytogenetic and biological properties. 2563 72


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