The XLR gene family consists of approximately 10 X-linked genes, the expression of which is regulated in lymphocyte development. Certain members of the gene family are closely linked to the murine xid immune deficiency mutation. Sequence analysis of a cDNA clone pM1 derived from the plasmacytoma MOPC167 showed an open reading frame capable of coding for a protein of 208 amino acids and mol wt 24,000. The lack of a signal peptide or transmembrane region indicates a probable cytoplasmic or nuclear localization for the predicted pM1 protein. The predicted protein shares significant homology with lamins A and C and other members of the intermediate filament family of proteins, and shares features important for the coiled-coil structure proposed for these proteins. Analysis of cDNA clones derived from a presecretory lymphoma and from adult thymus indicates that B and T lymphocytes transcribe a common major mRNA identical to pM1, while other rare transcripts were also identified by these studies. A series of clonal T lymphoma lines representing distinct stages of thymic differentiation showed that, as with B lymphoid tumors, XLR expression is correlated with the maturation of the thymomas.
The polycation poly(ethylenimine) (PEI) was used to deliver the plasmids coding for various combinations of caspases to Cox-2 overexpressing cancer cell lines. It was found that the expression of the delivered genes, controlled by the Cox-2 promoter, correlated with the expression of the endogenous Cox-2 gene in each cell line in a relatively linear manner. Among the various caspase combination regimens, the combination of caspase 3 plus caspase 9 proved to be the most effective because of an apparent synergy between the two gene products, and produced phosphatidylserine flipping in addition to fragmentation of genomic DNA. Caspase 1 appeared to work independently of either caspases 3 or 9, as no synergistic effect was observed. Transfections with genes coding for granzyme B and caspase 8 yielded a lesser amount of cell death. The delivery of a combination of caspase genes could be readily moved to in vivo research of bladder and colon cancer treatments, and holds great applicability to a wide array of additional tumor types.
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