Search results for: WM_45
#22719872 2012/06/12 To Up
High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.
Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2)/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15). Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p = 0.001), p21(Cip1/WAF1) (p = 0.003), p53 (p = 0.025). Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001), ulceration (p = 0.005) and poor disease-free survival (p = 0.008). Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53), WM45.1(MUTp53) and LOX(WTp53), further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1)/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.Gry Irene Magnussen, Ruth Holm, Elisabeth Emilsen, Anne Katrine Ree Rosnes, Ana Slipicevic, Vivi Ann Flørenes
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#10628399 // To Up
Association of EGFR gene fragments with nuclear matrix proteins in high and low metastatic melanoma cell lines.
Two melanoma cell lines with different metastatic potential were used to study the association of EGFR gene fragments with the nuclear matrix and its role in cancer metastasis by polymerase chain reaction. A 940 bp positive amplification by PCR using primers I-II was demonstrated in a high metastatic cell line, WM451. A 110 bp positive amplification was shown using primers III-IV in both high and low metastatic cell lines. This finding demonstrates that EGFR gene fragments are tightly bound to the nuclear matrix and suggests that binding ability of this EGFR gene fragment to nuclear matrix seems to be closely related to metastatic potential in melanoma cell lines WM45 1 and WM35.Z H Wang, M X Ding, M L Jin, S B Cheng-Chew, J P Yun, B Q Wu, E C Chew
1264 related Products with: Association of EGFR gene fragments with nuclear matrix proteins in high and low metastatic melanoma cell lines.
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