We have generated transgenic mice that express green fluorescent protein (GFP) under the control of the mouse insulin I gene promoter (MIP). The MIP-GFP mice develop normally and are indistinguishable from control animals with respect to glucose tolerance and pancreatic insulin content. Histological studies showed that the MIP-GFP mice had normal islet architecture with coexpression of insulin and GFP in the β-cells of all islets. We observed GFP expression in islets from embryonic day E13.5 through adulthood. Studies of β-cell function revealed no difference in glucose-induced intracellular calcium mobilization between islets from transgenic and control animals. We prepared single-cell suspensions from both isolated islets and whole pancreas from MIP-GFP-transgenic mice and sorted the β-cells by fluorescence-activated cell sorting based on their green fluorescence. These studies showed that 2.4 ± 0.2% ( n = 6) of the cells in the pancreas of newborn (P1) and 0.9 ± 0.1% ( n = 5) of 8-wk-old mice were β-cells. The MIP-GFP-transgenic mouse may be a useful tool for studying β-cell biology in normal and diabetic animals.

c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma

Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, cell proliferation, and invasion. These results establish an important role for paxillin in lung cancer. [Cancer Res 2008;68(1):132-42]

The MAPKs each demonstrate a specific cellular distribution after ischemia, and ERK and p38 are linked to apoptosis. Blockade of p38 or ERK provides significant protection from ischemic damage, suggesting a novel therapeutic role for MAPK inhibition in neuroprotection.

Background: Lamellipodia structures provide a platform for the spatio-temporal localization of key components necessary for cell migration. Results: HGF activates c-Met/PI3k/Akt signaling axis, which is essential for the recruitment of actin, cortactin, p47phox , and Rac1and ROS production in lamellipodia. Conclusion: HGF-induced spatio-temporal localization of cytoskeletal proteins and NADPH oxidase components regulate lamellipodial ROS and cell migration. Significance: This study identifies a novel role for lamellipodial ROS in cell motility.