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1.  SWAP-70: A New Type of Oncogene 
PLoS ONE  2013;8(3):e59245.
SWAP-70 is a protein that has been suggested to be involved in regulation of actin rearrangement. Having discovered that an artificially-derived mutant of SWAP-70 can transform mouse embryo fibroblasts, we searched for naturally-occurring mutations in the SWAP-70 gene, finding listings for several on the Web at, including three mutations found in ovarian cancers. (The number of such mutations has now reached 13 out of 228 tumors). We created expression vectors for the mutant SWAP-70 proteins and introduced these into NIH3T3 cells. The cells expressing the mutant SWAP-70 constructs exhibited faster growth than the parental or wild-type SWAP-70-expressing cells. In most instances, cells that are able to grow in soft agar will form tumors in nude mice. While SWAP-70-transformed cells grew in soft agar, they failed to form tumors in nude mice. This result implies that transformation by the SWAP-70 mutants is unique. The cells bearing the mutant SWAP-70 genes were sensitive to nutrient starvation, supporting the idea that they are transformed cells. However, they failed to pile up and demonstrated contact inhibition, unlike most normal transformed cells. Upon expression of human SWAP-70 genes, MEK1 was activated. This activation appeared to contribute to the saturation density of the cells. As SWAP-70 has been shown to be the last protein to receive signals from cytokines, it is likely that there is a putative feedback signaling pathway, and that disorder of this signaling pathway can transform cells. Accordingly, this may explain why SWAP-70-transformed cells have different characteristics than most transformed cells.
PMCID: PMC3595256  PMID: 23555004
2.  Scattering of MCF7 Cells by Heregulin ß-1 Depends on the MEK and p38 MAP Kinase Pathway 
PLoS ONE  2013;8(1):e53298.
Heregulin (HRG) β1 signaling promotes scattering of MCF7 cells by inducing breakdown of adherens and tight junctions. Here, we show that stimulation with HRG-β1 causes the F-actin backbone of junctions to destabilize prior to the loss of adherent proteins and scattering of the cells. The adherent proteins dissociate and translocate from cell–cell junctions to the cytosol. Moreover, using inhibitors we show that the MEK1 pathway is required for the disappearance of F-actin from junctions and p38 MAP kinase activity is essential for scattering of the cells. Upon treatment with a p38 MAP kinase inhibitor, adherens junction complexes immediately reassemble, most likely in the cytoplasm, and move to the plasma membrane in cells dissociated by HRG-β1 stimulation. Subsequently, tight junction complexes form, most likely in the cytoplasm, and move to the plasma membrane. Thus, the p38 MAP kinase inhibitor causes a re-aggregation of scattered cells, even in the presence of HRG-β1. These results suggest that p38 MAP kinase signaling to adherens junction proteins regulates cell aggregation, providing a novel understanding of the regulation of cell–cell adhesion.
PMCID: PMC3538754  PMID: 23308187
3.  Heregulin β-1 Induces Loss of Cell-Cell Contact and Enhances Expression of MUC1 at the Cell Surface in HCC2998 and MKN45-1 Cells 
PLoS ONE  2011;6(12):e29599.
Signal transduction and cell responses after stimulation with heregulin β-1 (HRG) are examined in HCC2998 and MKN45-1 cells, which have been used for a model system to study the formation of signet ring carcinomas, one of poorly differentiated adenocarcinomas. HRG stimulation causes rounding of the cells, responding to HRG. The adherens junction, which is present in the control cells, is disrupted and cell-cell interaction is lost after stimulation. Inhibition of phosphatidylinositol (PI)-3 kinase or p38 MAP kinase blocked this reaction, which indicates that the PI-3 kinase-p38 MAP kinase pathway is required for this reaction. Inhibition of the p38 MAP kinase pathway resulted in immediate restoration of cell-cell interaction. This result indicates that signaling for adherent molecules is strictly regulated by growth factor signaling. Expression of MUC1 at the cell surface is also observed and found to be expressed only after HRG stimulation. The total amount of MUC1 remains unchanged, suggesting that this amount is not due to induction of gene expression but to translocation of MUC1 from the inner membrane to the plasma membrane. This reaction is independent of the cytohesin pathway but dependent on PI-3 kinase activity. In addition to these reactions, HRG stimulates cell growth of both HCC2998 and MKN45-1 cells, depending on the ERK pathway given that the MEK inhibitor abolishes this effect. Therefore, HRG induces various reactions in HCC2998 and MKN45-1 cells by different pathways. These reactions are all related to characteristics of tumors, which implicates that HRG signaling can contribute to the formation of tumors.
PMCID: PMC3245292  PMID: 22216327
4.  Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis 
Science (New York, N.Y.)  2007;315(5809):207-212.
We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ~160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
PMCID: PMC2080659  PMID: 17218520
Genomics  2006;89(2):291-299.
BAC libraries generated from restriction-digested genomic DNA display representational bias and lack some sequences. To facilitate completion of genome projects, procedures have been developed to create BACs from DNA physically sheared to create fragments extending up to 200 kb. The DNA fragments were repaired to create blunt ends and ligated to a new BAC vector. This approach has been tested by generating BAC libraries from Drosophila DNA, with average insert lengths between 50 – 150 kb. The libraries lack chimeric clone problems as determined by mapping paired BAC-end sequences to the assembled fly genome sequence. The utility of “sheared” libraries was demonstrated by closure of a previous clone gap and by isolation of clones from telomeric regions, which were notably absent from previous Drosophila BAC libraries.
PMCID: PMC1909752  PMID: 17098394
bacterial artificial chromosome; BAC; sheared DNA; cloning; vector; adaptor; telomere; centromere and heterochromatin

Results 1-5 (5)