PubMed · 4968805
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H L Moffet, A C Siegel, H K Doyle. 1968. Nonstreptococcal pharyngitis.. https://doi.org/10.1016/s0022-3476(68)80038-1
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A variety of transcription factors are post-translationally modified by SUMO, a 97-residue ubiquitin-like protein bound covalently to the targeted lysine. Here we describe SUMO modification of the Ets family member ERM at positions 89, 263, 293, and 350. To investigate how SUMO modification affects the function of ERM, Ets-responsive intercellular adhesion molecule 1 (ICAM-1) and E74 reporter plasmids were employed to demonstrate that SUMO modification causes inhibition of ERM-dependent transcription without affecting the subcellular localization, stability, or DNA-binding capacity of the protein. When the adenoviral protein Gam1 or the SUMO protease SENP1 was used to inhibit the SUMO modification pathway, ERM-dependent transcription was de-repressed. These results demonstrate that ERM is subject to SUMO modification and that this post-translational modification causes inhibition of transcription-enhancing activity.
A novel second generation retroviral producer cell strategy (an adenoviral/retroviral combined delivery system) has been developed by this laboratory. In the present studies, this delivery system was used to examine its delivery efficiency in vitro and in vivo by using a marker gene, LacZ, and a therapeutic gene, herpes simplex virus thymidine kinase (HSV-tk), both of which were transduced into a tumor cell line KBALB. In the in vitro experiments for delivery efficacy of the LacZ gene, the delivery efficiency of KBALB+KBALBLNPOZAdN/H (1:1) was 27.8% higher than that of KBALB+KBALBLNPOZ (1:1) (P<0.01). For the antitumor effect of HSV-tk/ganciclovir (GCV), the death ratio of KBALB+KBALBLNCTKAdN/H (1:1) was higher than that of KBALB+KBALBLNCTK (1:1), on 4, 6, and 8 days at a concentration of 0.1, 1, and 10 microg/ml, respectively (P<0.01 or P<0.05). In the in vivo experiments for LacZ gene expression, the delivery efficiency in KBALB+KBALBLNPOZAdN/H (1:1) was 21.5% more efficient than that in KBALB+KBALBLNPOZ (1:1) (P<0.01). For HSV-tk/GCV antitumor effect, the suppression of tumors by KBALB+KBALBLNCTKAdN/H (1:1) was more effective than that by KBALB+KBALBLNCTK (1:1) (P<0.05). Results suggest that this new delivery system is more efficient than the traditional in vitro and in vivo retroviral vector delivery system.
Co-transfer of immunomodulatory and antiproliferative genes may be the basis for new strategies to potentiate tumor regression. In this study, we evaluated the in vitro effect of the introduction of human wild-type p53, granulocyte-macrophage colony-stimulating factor (GM-CSF), and B7-1 genes via recombinant adenovirus on the growth and immunogenicity of Hep-2 or primary laryngeal cancer cells. By the introduction of wild-type p53 gene, the growth of Hep-2 cells was inhibited via enhanced apoptosis. By the introduction of GM-CSF and B7-1 genes, the immunogenicity of cancer cells was enhanced. Significant proliferation of tumor infiltrating lymphocytes (TILs) and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) were induced in vitro. Furthermore, the combinative effect of GM-CSF and B7-1 was even more evident than that of any one of them singly. These results suggest that the co-transfer of human wild-type p53, GM-CSF and B7-1 genes into tumor cells via recombinant adenovirus may be further developed into a potential combination gene therapy strategy for cancer.