We have observed that aggregation of human platelets, caused by activation of integrin ␣ IIb  3 and its consequent binding of fibrinogen, stimulates a novel pathway for synthesis of phosphatidylinositol 3,4-bisphosphate, thereby activating protein kinase B/Akt. Such synthesis depends upon both the generation of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin (IC 50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by PtdIns3P 4-kinase. We now report that a recently characterized C2 domain-containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely to be responsible for the stimulated synthesis of PtdIns3P observed in platelets. HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is sensitive to wortmannin (IC 50 6 -10 nM), requires Mg 2؉ , and shows strong preference for PtdIns over PtdIns4P or phosphatidylinositol 4,5-bisphosphate as substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an ␣ IIb  3 -dependent manner or when platelet or CHRF-288 lysates are incubated with Ca 2؉ . Activation is prevented by calpain inhibitors. CHRF-288, which cannot undergo activation of ␣ IIb  3 and thereby aggregate in response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may thus be an important effector for integrin-dependent signaling.
Titanium and its alloys are used worldwide in surgery. Dental implants, screws and plates, prostheses, and surgical instruments are made with titanium-based metals. The favorable characteristics that make this material desirable for implantation are (a) mechanical proprieties and (b) biocompatibility. The latter has been demonstrated by in vivo studies with animal models and clinical trials over a 40-year period. However, the exact effect of titanium on cells is still not well characterized. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of gene expression in a cell system. Several genes whose expression was significantly up- or downregulated in an osteoblast-like cell line (MG-63) on titanium were identified with the use of DNA microarrays containing 19,200 genes. The differentially expressed genes are associated with a broad range of functional activities, including apoptosis, vesicular transport, and structural function. It was also possible to detect some genes whose function is unknown. The data reported are, to the author's knowledge, the first genetic portrait of titanium-cell interaction. They may help to provide a better understanding of the molecular mechanisms of titanium biocompatibility and serve as a model for studying the biocompatibility of other materials.
Odontogenic tumors are rare neoplasms arising from the odontogenic apparatus. We aimed to identify molecular characteristics associated with odontogenic tumorigenesis and malignancy. To this end, we investigated the expression level of human genes by using, for the first time in odontogenic tumors, the technique of expression profiling. Gene expression alterations common to all six odontogenic tumors were identified by the use of cDNA microarrays containing 19,000 human cDNAs. Statistical analysis on a subset of 4974 cDNAs present in the biopsies identified 506 distinct genes associated with the tumors (p-value < 0.01). Gene ontology analysis of the cellular processes which were differentially regulated in odontogenic tumors was accomplished by the use of a subset of 1409 annotated genes. Finally, 43 cDNAs differentiated the three malignant odontogenic tumors (ameloblastic carcinoma, clear cell odontogenic tumor, granular cell odontogenic tumor) from the three benign ameloblastoma biopsies (p < 0.01). The identified genes might help us better classify borderline odontogenic tumors.
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