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  • Title: The low molecular weight cyclin E isoforms augment angiogenesis and metastasis of human melanoma cells in vivo.
    Author: Bales E, Mills L, Milam N, McGahren-Murray M, Bandyopadhyay D, Chen D, Reed JA, Timchenko N, van den Oord JJ, Bar-Eli M, Keyomarsi K, Medrano EE.
    Journal: Cancer Res; 2005 Feb 01; 65(3):692-7. PubMed ID: 15705861.
    Abstract:
    Immunohistochemical analysis has consistently shown that cyclin E is up-regulated in human malignant melanomas in vivo. Here we analyzed such expression in more detail and show that cyclin E is overexpressed and present in low molecular weight (LMW) isoforms in metastatic melanoma and in a subset of primary invasive melanoma tumor tissues, but not in benign nevi. Human metastatic melanoma cell lines, but not normal melanocytes, also expressed the LMW cyclin E forms. The biological significance of these findings was established by showing that overexpression of two LMW cyclin E forms named cyclin E truncated 1 [cyclinE(T1)] and cyclin E truncated 2 [cyclinE(T2)] in a low tumorigenic and non-metastatic primary cutaneous melanoma cell line generated angiogenic tumors with prominent perineural invasion compared with full-length cyclin E. In addition, cyclin E(T1)- and cyclin E(T2)-expressing melanoma cells displayed a dramatic increase in the incidence and number of metastases in an experimental lung metastasis assay. Together, these results indicate that the LMW cyclin E forms are functional and likely act as regulators of human melanoma tumor progression and invasion.
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