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The contribution of the mRNA cap-binding protein, eIF-4E, to malignant transformation and progression has been illuminated over the past decade. eIF-4E overexpression has been demonstrated in human tumors of the breast, head and neck, colon, prostate, bladder, cervix and lung, and has been related to disease progression. Overexpression of eIF-4E in(More)
A central issue in the study of neoplastic transformation is to understand how proto-oncogene products deregulate normal processes of cell growth and differentiation: an intrinsic aspect of this is to probe the sequence of events leading to altered expression of proto-oncogenes. In the past few years, studies aimed at understanding the regulation and(More)
Head and neck squamous cell cancers (HNSCC) have a high local recurrence rate due to incomplete tumor resection. The use of molecular markers to establish surgical margins may decrease local recurrence. Surgical margins are determined by histopathologic analysis on frozen sections. We postulate that genetic and molecular changes precede gross histologic(More)
The eukaryotic translation initiation factor eIF-4E binds to the cap structure of mRNAs as one component of the eIF-4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of eIF-4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of(More)
Angiogenesis is the formation of new blood vessels from the existing vasculature. Vascular endothelial growth factor (VEGF) is an endothelium-specific angiogenic factor strongly implicated in pathological angiogenesis. In this study, the mRNA and protein expression of the four alternatively spliced VEGF isoforms (121, 165, 189 and 206 amino acids) were(More)
BACKGROUND Eukaryotic initiation factor 4E (eIF-4E) is a 25-kilodalton phosphoprotein that binds specifically to mRNA as the initial step for mRNA translation. An elevated level of eIF4E has been associated with the up-regulation of various protooncogene products. Transfection of cell lines by viral vectors with eIF4E overexpression has resulted in(More)
The gene Tousled of Arabidopsis Thaliana encodes a protein kinase which, when mutated, results in abnormal flower development. From a library of mRNAs that are translationally upregulated by overexpression of the translation initiation factor 4E, we identified a mammalian Tousled Like kinase (TLK1B). The human TLK1B mRNA contains a 5'UTR 1088-nt-long with(More)
BACKGROUND The overexpression of eukaryotic initiation factor 4E (eIF4E), which is a critical component of the RNA helicase complex important in the translation of messenger RNAs with long and/or complex 5' untranslated regions, appears to impact malignant transformation and predict cancer recurrence in patients with breast cancer, independent of nodal(More)
BACKGROUND The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila, or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and chromosome missegregation probably due to(More)
The regulation of androgen receptor (AR) expression in prostate cancer is still poorly understood. The activation of the epidermal growth factor receptor (EGFR) in prostate cancer cells was previously shown to lower AR expression by a rapamycin-sensitive, posttranscriptional mechanism involving the AR mRNA 5'-untranslated region (5'-UTR). In a search for an(More)