Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that insulin-like growth factor-binding protein (IGFBP-2), a modulator of the actions of IGFs, also has IGF-independent effects in human tumor cell lines. These involve specific binding of IGFBP-2 to alpha5beta1-integrin, followed by alterations in the phosphorylation status of downstream signaling molecules. Previously, IGFBP-2 has also been shown to be associated with cell proliferation, adhesion and migration. Here, we investigated direct effects of IGFBP-2 on apoptosis and alterations in the expression of related proteins. The breast cancer cell line Hs578T, which shows no IGFBP-2 production of its own and is independent of the IGF-I receptor, was treated with human recombinant IGFBP-2 in order to study the changes in gene expression induced by IGFBP-2. The methods employed for this purpose were oligonucleotide microarrays, real-time RT-PCR, western blotting, and immunoassays. Out of the 440 genes covered by the Oligo GEArray Human Cancer Microarray OHS-802, the expression of 77 genes was directly influenced by IGFBP-2. By the use of real-time quantitative RT-PCR, the gene expression of Nuclear Factor (NF)kappaB, p53, transforming growth factor beta (TGF beta-1), LAMB1 (Laminin, Beta 1), Bcl-2, and IIp45 was found to be significantly upregulated (by 1.2- to 3.05-fold; all P < 0.001). Accordingly, NFkappaB, p53, and TGF beta-1 proteins, as measured by Western blotting and immunoassay, were upregulated > 1.5-fold. By using an ELISA-based and a flow cytometry-based apoptosis assay, IGFBP-2 was found to have a pro-apoptotic effect on Hs578T cells. Our results suggest that IGFBP-2-induced gene expressions are of functional significance for proliferation, cell adhesion, cell migration and apoptosis, and showed that IGFBP-2 can promote apoptosis in tumor cells independent of IGF.
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PMID:IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. 1690 20

Human adult bone marrow-derived neural stemlike cells (MDNSCs) may serve as ideal seed cells for cell replacement therapy for human neurological disorders and injuries. However, the long-term safety of this cell population after transplantation must be thoroughly explored before clinical application, and tumorigenicity is a major concern. In this study, we generated MDNSCs capable of forming neurospherelike aggregates and with the potency to differentiate into neural lineage cells in vitro and investigated hundreds of cancer-related genes in MDNSCs in order to determine whether there were any characteristics that could help in the evaluation of their tumorigenic potential. According to the results of testing by PCR and DNA sequencing, there were no mutations at the frequent mutation sites of tumor-suppressor genes p53, p16, and Rb1. Of the 440 cancer-related genes covered by Oligo GEArray Human Cancer Microarray OHS-802, 63 were found to be significantly overexpressed compared with that in fresh normal human adult bone marrow depleted of red blood cells (RBCs). In particular, the overexpressed genes included those promoting cell proliferation and cell invasion and metastasis and members of several oncogenic signaling pathways. The overexpression of MYC, MMP2, Notch2, STC1, ITGA3, STAT5b, RhoC, and Wnt1 was also revealed by quantitative real-time RT-PCR. Because it has been shown that activation of some of these genes promote tumorigenesis, our findings highlight the need for further studies of long-term tumorigenicity in MDNSCs.
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PMID:Expression profile of cancer-related genes in human adult bone marrow-derived neural stemlike cells highlights the need for tumorigenicity study. 1763 1