HER2/Neu is overexpressed in 25 ± 30% of all human breast cancers as a result of both gene ampli®cation and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6 ± 8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neuoverexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These ®ndings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins a ecting its regulation are appropriate therapeutic targets.

Bilateral decompression of lumbar spinal stenosis via a unilateral approach involves shorter operating times and less blood loss, less muscle dissection, fewer and less severe complications, and better mobility in the immediate postoperative period than open decompressive techniques. In addition, this technique is very similar to the commonly performed microendoscopic discectomy and is easily mastered over time.

Dry beans lower plasma cholesterol, an effect that has been associated with both the fiber and the protein content of beans. The objective of this study was to determine the acute hormone and lipid responses to a test meal that contained dry beans as a source of dietary fiber. A crossover design was employed in which men consumed the test meal and a control meal in random order. Both meals contained egg, bread, jelly, orange juice, milk and margarine. The high fiber meal contained white beans, whereas the low fiber (control) meal contained rice and dry milk. The men maintained their normal dietary pattern and fasted overnight before the study days. After a fasting blood sample was drawn, the men consumed the test meal and blood samples were collected over the next 6 h. Blood samples were analyzed for cholecystokinin (CCK), insulin and glucose. Plasma was separated into lipoprotein fractions and the triglyceride, cholesterol, apolipoprotein (apo) B100 and B48 content of triglyceride-rich lipoproteins determined. Insulin and glucose responses did not differ significantly between test meals; however, the CCK response was twice as high after the bean-containing meal than after the low fiber meal (P = 0.03). The increase in apo B48 concentration was significantly higher after the bean meal than after the low fiber meal (P < 0.05). Adding beans to a meal to increase fiber content prolongs the postprandial presence of intestinally derived lipoproteins and augments the CCK response to the meal.

Rats were fed a fiber-free (FF) mixture or the same diet with a supplement of 20% wheat bran (WB). After 2 weeks, the pancreas contained higher levels of amylase and trypsin in rats fed WB. In response to a meal, the intestine contained more lipase activity in the WB group. The dry weight of material and protein level in the intestinal contents were also elevated in the WB group. The size of the intestinal villi had not changed, but it did contain more goblet cells. The results indicate that consumption of wheat bran can lead to changes in the exocrine pancreas, perhaps associated with shifts in gut hormones, and may effect absorption by increasing the bulk of material as well as enhancing mucus production in the intestine.