128 research outputs found
Transcriptional activation of signal transducer and activator of transcription (STAT) 3 and STAT5B partially mediate homeobox A1-stimulated oncogenic transformation of the immortalized human mammary epithelial cell
No full textWe have previously demonstrated that the p44/42 MAPK pathway is one pathway involved in homeobox (HOX) A1-stimulated oncogenesis. However, inhibition of MAPK kinase 1 does not completely prevent HOXA1-stimulated oncogenic transformation, suggesting the involvement of additional signal transduction pathways. Here, we report that forced expression of HOXA1 in immortalized human mammary epithelial cells significantly increased levels of signal transducer and activator of transcription (STAT) 3, 5A, and 5B mRNA by transcriptional up-regulation. The protein levels of STAT3 and 5B, but not STAT5A, and protein phosphorylation levels of STAT3 and 5B were significantly increased by forced expression of HOXA1. Forced expression of STAT3 or STAT5B was sufficient to transform oncogenically an immortalized human mammary epithelial cell line. Accordingly, inhibition of STAT3 or STAT5B activity with dominant negative STAT3 or STAT5B abrogated the ability of HOXA1 to stimulate cell proliferation, survival, oncogenic transformation, and generation of large disorganized multiacinar structures in three-dimensional culture. These results suggest that HOXA1 partially mediates oncogenic transformation of the immortalized human mammary epithelial cell through modulation of the STAT3 and STAT5B pathways
p73 independent of c-Myc represses transcription of platelet-derived growth factor beta-receptor through interaction with NF-Y
No full textWe recently reported that c-Myc represses the transcription of platelet-derived growth factor (PDGF) beta-receptor (Izumi, H., Molander, C., Penn, L. Z., Ishisaki, A., Kohno, K., and Funa, K. (2001) J. Cell Sci. 114, 1533-1544). We demonstrate here that the p53 family protein p73alpha represses PDGF beta-receptor transcription essentially by the same mechanism. p73alpha but not p73beta or p53 represses the transcription in concordance with its ability to bind NF-YC and NF-YB. None of other p73 isoforms (i.e. p73beta, p73gamma, p73epsilon), C-terminal deletion mutants of p73alpha, and p53 is able to bind NF-Y with the exception of p63alpha. This finding suggests that the sterile alpha-motif domain present only in p73alpha and p63alpha is the interaction site. For the repression, the N-terminal transactivation domain of p73alpha is also indispensable, arguing for the importance of the activity of p73alpha in the mechanism. p73alpha binds the C-terminal HAP domain of NF-YC previously found to be the interaction site with c-Myc and TBP. Because c-Myc induces and activates p73alpha (Zaika, A., Irwin, M., Sansome, C., and Moll, U. M. (2001) J. Biol. Chem. 276, 11310-11316) and they bind each other (Uramoto, H., Izumi, H., Ise, T., Tada, M., Uchiumi, T., Kuwano, M., Yasumoto, K., Funa, K., and Kohno, K. (2002) J. Biol. Chem. 277, in press), we examined whether the repression by p73 is dependent on c-Myc. However, Myc-null rat fibroblasts are also susceptible to p73alpha-induced repression. Serum stimulation of NIH3T3 cells gradually decreased the amount of endogenous NF-Y binding to the PDGF beta-receptor promoter, whereas NF-YA expression in the nuclear extracts remains unchanged. Our results indicate that serum stimulation induces c-Myc and p73alpha, leading to the down-regulation of PDGF beta-receptor expression by repressing its transcription
Scattering theory for the Dirac equation of Hartree type in 2+1 dimensions
No full textConsider a scattering problem for the Dirac equation with a nonlocal term including the Hartree type in two dimensions. We show the existence of scattering operators for small data in the subcritical and critical Sobolev spaces
Study on Physicochemical Properties and its Effective Use of Asphalt Pavement Cutting Waste Water
No full textAbstractWhile cutting asphalt pavement surfaces, cooling water is continuously given to the cutting machine blades to prevent the heat increase and to control the scatter of cutting dusts. As the results, asphalt pavement cutting waste water is generated. The amount of waste water generated at one construction site is by no means a lot, however, the water quality is not environmentally friendly. In view of above, the physical and chemical properties of cutting waste water were first investigated. Then the possibility of effective use of the cutting waste water was investigated using flocculants and granulation technique. The results show that the waste water quality can be improved by the effects of flocculants. Mud sediments after flocculated in the waste water can be granulated and the granules may be used as recycled sands or recycle crusher-runs aggregates
Identification of a 450-kDa Human Epidermal Autoantigen as a New Member of the Plectin Family
No full textThe serum from an individual with a subepidermal blistering disease was previously shown to recognize a 450-kDa epidermal autoantigen. The molecular structure of this antigen was investigated by screening a human keratinocyte cDNA library with the patient's serum. One clone, with a 276-bp cDNA insert, that encoded an epitope recognized by the serum was isolated. Rabbit polyclonal antibodies that were prepared against the corresponding fusion protein recognized the 450-kDa epidermal antigen and stained the basal keratinocytes in human epidermis. This clone was used for further screening of the original keratinocyte and HeLa cell cDNA libraries. Two different, but closely related, 0.8- and 2.0-kb cDNAs were isolated, and their deduced amino acid sequences indicated that the encoded proteins belonged to the plectin family. Northern blot analysis of total RNA from human keratinocytes with these cDNA inserts as probes detected RNAs of ∼12–13 kb. The 0.8-kb cDNA hybridized to polyadenylated RNA species from human skeletal muscle, heart, lung, and kidney, whereas the 2.0-kb cDNA hybridized to transcripts present only in kidney and lung. Southern blot analysis of genomic DNA from the human placenta revealed similar, but not identical, patterns of hybridization with the 0.8- and 2.0-kb cDNAs. Data suggest that the 0.8- and 2.0-kb cDNAs encode two different proteins but are derived from the same gene
Clinical implication of cyclosporin for systemic autoimmune diseases: relevance to multidrug resistance
No full text
Analysis of 8-hydroxyguanine in rat kidney genomic DNA after administration of a renal carcinogen, ferric nitrilotriacetate
No full textRapid turnover of low density lipoprotein receptor in human monocytic THP-1 cells
No full textAbstractWe examined whether human monocyte-derived macrophages had low density lipoprotein (LDL) receptors with a short life span. The human monocytic leukemia cell line, THP-1, was highly differentiated when treated with phorbol ester. LDL receptors degraded rapidly with half-lives of 3–4 h in THP-1 cells before phorbol ester treatment. During the transition into monocytic cells, expression of the LDL receptor gene was not affected. However, relative degradation rates of LDL receptors normalized by those of cellular total proteins were about twice as fast in phorbol ester-treated THP-1 cells compared to untreated cells
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