Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT-PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21 WAF1 , MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.
Gold nanoprobes immobilized with fluorescein‐hyaluronic acid (HA) conjugates are fabricated and utilized for monitoring intracellular reactive oxygen species (ROS) generation in live cells via nanoparticle surface energy transfer. A bio‐inspired adhesive molecule, dopamine, is used to robustly end‐immobilize HA onto the surface of gold nanoparticles (AuNPs) for securing intracellular stability against glutathione. ROS induces cleavage and fragmentation of the HA chains immobilized on the surface of the AuNPs allows rapid and specific detection of intracellular ROS by emitting strong fluorescence‐recovery signals. In particular, fluorescence‐quenched gold nanoprobes exhibit selective and dose‐dependent fluorescence‐recovery signals upon exposure to certain oxygen species such as superoxide anion (${\rm O}_{2}^{\cdot{{-\!\!\!\!\!-}}}$) and hydroxyl radical (·OH). The fluorescent gold nanoprobe is usefully exploited for real‐time intracellular ROS detection and antioxidant screening assay, and has exciting potential for various biomedical applications as a new class of ROS imaging probes.
When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2α phosphorylation. Transcription of two downstream targets of eIF2α, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuro-
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