Magic™ Anti-JUND (Phospho S255) monoclonal antibody, clone FQS7572(3)

Menin (MEN1) is atumor-suppressor protein in neuroendocrine tissue. Therefore, we tested the novel hypothesis that menin regulates cholangiocarcinoma proliferation. Menin and miR-24 expression levels were measured in the following intrahepatic and extrahepatic cholangiocarcinoma (CCA) cell Lines, Mz-ChA-1, TFK-1, SG231, CCLP, HuCCT-1, and HuH-28, as well as the nonmalignant human intrahepatic biliary tine, H69. miR-24 miRNA and menin protein levels were manipulated in vitro in Mz-ChA-1 cell lines. Markers of proliferation and angiogenesis (Ki-67, vascular endothelial growth factors A/C, vascular endothelial growth factor receptors 2/3, angiopoietin 1/2, and angiopoietin receptors 1/2) were evaluated. Mz-ChA-1 cells were injected into the flanks of nude mice and treated with miR-24 inhibitor or inhibitor scramble. Menin expression was decreased in advanced CCA specimens, whereas miR-24 expression was increased in CCA. Menin overexpression decreased proliferation, angiogenesis, migration, and invasion. Inhibition of miR-24 increased menin protein expression while decreasing proliferation, angiogenesis, migration, and invasion. miR-24 was shown to negatively regulate menin expression by luciferase assay. Tumor burden and expression of proliferative and angiogenic markers was decreased in the miR-24 inhibited tumor group compared to controls. Interestingly, treated tumors were more fibrotic than the control group. miR-24 dependent expression of menin may be important in the regulation of nonmalignant and CCA proliferation and may be an additional therapeutic tool for managing CCA progression.

The transcription factor deltaFosB (Delta FosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of Delta FosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. Delta FosB immunoreactivity (ir) was increased in the MPOA of previously naive and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35-37-kDa isoform of Delta FosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase Delta FosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing Delta FosB, its dominant negative antagonist Delta JunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. Delta FosB overexpression impaired copulation and promoted female-directed aggression, compared to Delta JunD and control males. These data suggest that Delta FosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression.